Title of Invention

PROCESS FOR PREPARING ALKYL-(R)-4-CYANO-3 HYDROXYBUTANOATE,IMPORTANT INTERMEDIATES IN THE SYNTHESIS OF ANTIHYPERLIPOPROTEINEMIC AGENTS

Abstract

A process for preparation of chiral synthones of formula VI, Where, R is a C1-4 alkyl group. for statin synthesis using Glucono delta lactone as a starting material. The process comprises the Oxidising Glucono delta, lactone, treating the oxidized with a metal hydroxide to obtain a metal salt, treating the metal salt with an inorganic acid and further treatment with an alcohol, a second organic acid and a cyanide compound to obtain the chiral synthone.

Full Text

FORM-2 THE PATENT ACT, 1970 (39 of 1970) & THE PATENT RULES, 2003 COMPLETE SPECIFICATION (See section 10 and Rule 13) A PROCESS FOR PREPARATION OF A CHIRAL INTERMEDIATE M. J. INSTITUTE OF RESEARCH A Research Institute organized under the laws of India of 113, Jolly Maker Chambers-II, Nariman Point, Mumbai-400 021, Maharashtra, India. THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED. Field Of Invention: The present invention relates to a process for preparation of a chiral intermediate. Particularly, the present invention relates to a synthetic process for preparation of a chiral intermediate used in the synthesis of Cholesterol lowering drugs. More particularly, the present invention relates to a process for the preparation of a chiral intermediate for the synthesis of HMG-CoA reductase inhibitors. Definitions: As used in the present specification, the following words and phrases are generally intended to have the meanings as set forth below, except to the extent that the context in which they are used indicates otherwise. 'Alkyl means a hydrocarbon group of 1 to 4 carbon atoms such as methyl, ethyl, propyl, butyl, isopropyl. Alkali or Alkaline earth metal means metal elements in group IA, IIA of the periodic table i.e. sodium, potassium, lithium, calcium, barium, magnesium and the like. DM means dematerialized water. DMF means N,N-dimethylformamide or dimethylformamide. DMSO means Dimethyl sulfoxide. Synthon means a structural unit within a molecule which is related to a possible synthetic operation. Statins means HMG-CoA reductase inhibitors also known as hypolipidemic agents used for lowering blood cholesterol levels in humans. TLC is an abbreviation of 'thin layer chromatography'. 2 Background Of The Invention: Statin drugs like Atorvastatin and Rosuvastatin are completely synthetic molecules while some of the earlier statins were obtained from fermentation process or by preparing semi synthetic derivatives of such fermentation products. The synthetic statins share the chiral 3,5-dihydroxyacid side chain, which is also found in certain natural products and is essential for pharmacological activity. Synthesis of such a chiral side chain requires greater skill for its preparation. Prior Art: In the method described by RUFF published in Ber 1889, Vol 32, pp 3672 0 3675 and 1900, vol-30 pp 1798 - 1802, from an aldolic acid derivative of saccharide with n carbon atoms oxidized by hydrogen peroxide in presence of ferric ions to an aldose derivative with n-1 carbon atoms, however the yield is poor. In 1934 R. C. Hockett & C. S. Hudson and H.W. Diehl & C. S. Hudson published in J. Amer. Chem. Soc, vol 56, pp 1632-33 and in 1950 vol 72, pp 4546 respectively with ~ 35% to 45%) yield of aldose derivative. While starting with a gluconate salt. However, isolation of the product needs difficult purification operation which involves use of ion exchange resins and column chromatography. Methods known in prior art include use of 4 - chloroacetoacetic acid ethyl ester as the starting raw material which needs to be reduced asymmetrically by chemical, biochemical or other such methods. The chiral 4-chloro -3- hydroxybutanoate ester is then subjected to cyanation reaction to obtain the required chiral intermediate Ethyl - (R) - 4 - cyano -3 -hydroxy butanoate. However, the yield of cyanation reaction are generally low unless specific industrial design like a variable residence time reactor are employed [Proctor, L , e. News letter, June 2003, Highlights from the 7th International Conference on Organic Process Research and Development, New Orleans, March 16-19, (2003)]. Besides, this process necessitates use of asymmetric reduction techniques which are expensive. 3 Another process for the preparation of 4-chloro -3- hydroxybutanoic acid ester [Cho, S-W et. al. WO 2004 / 092114 Al, Oct 28, (2004)] reports reaction of epichlorohydrin with a metal cyanide in the first stage. The yield of an intermediate product 4-chloro -3-hydroxybutyronitrile can be controlled by controlling the pH of reaction medium at desired level in the range of 7.0 to 8.0, particularly between 7.3 to 7.8. Resultant 4-chloro -3-hydroxybutyronitrile, is next subjected to acid hydrosis, preferably in presence of an alcohol medium, to obtain an ester of 4-chloro -3- hydroxy butanoic acid i.e. the required .product. However, as inferred from this patent document, preparation of an optically active 4-chloro -3- hydroxybutanoic acid ester requires use of a chiral epichlorohydrin. This is a very expensive raw material. Since synthesis of chiral key intermediates of the statin drug substances like Atorvastatin requires chiral 4-chloro -3- hydroxybutanoic acid ester, the above process is economically less feasible. Furthermore, synthesis of the chiral synthon Alkyl, -(R)- 4 - cyano - 3 - hydroxybutanoate, from chiral 4-chloro -3- hydroxybutanoic acid ester arising from such a process needs variable residence time type specific reactor designs to achieve good yields. In addition to above process as known in the existing art, there are also reported biochemical methods which involve chemo-enzymatic, aldolase catalysed processes for enantioselective statin intermediates. [Greenberg, W.A. et. al, PNAS (USA), Vol. 101, No. 16, p.5788, (2004); Sakaguchi, K. et.al, JP 4124157, April 24, (1992); Junjie, L. et.al, Tetrahealron Lett, Vol. 45, p. 2439 (2004); Ohrlein, R. et.al. Adv. Synthesis and Catalysis, Vol.345, p.713,(2003).] Such enzymatic processes, in general, involve aldol type reactions, while utilizing DERA (i.e. Deoxyribose - 5 - phosphate - 5 - aldolase ). These processes employ smaller building blocks of two carbons atoms like chloroacetaldehyde, acetaldhyde and the like, which are sequentially condensed in presence of DERA and form the six carbon lactone intermediate. Such a lactone product is then be derivatised into the required chiral synthon , e.g. alkyl - (R) - 4 - cyano - 3 - hydroxybutanoate. Some of the chemo-enzymatic processes also report use of DERA mutants which are specifically developed to enhance its capability and utility in sequential aldol condensations. These DERA mutants perform more efficiently as compared to the wild type DERA. 4 Advantages like higher catalytic activity, better acceptability of the substrate molecules and the like were observed by researchers. Baker's yeast as well as several yeast strains have also been used for making the chiral synthon, 4 - chloro - 3 - hydroxybutanoate ethyl ester from ethyl - 4 - chloro acetoacetate. Certain research groups [Houng, J-Y et.al., Biotechnology Lett., Vol.25, p. 17,(2003)] have recently applied slow release biocatalysis methods, to achieve asymmetric reduction of ethyl -4 - chloroacetoacetate. The process employs Amberlite type resins which first absorb the substrate molecules i.e. 4 - chloroacetoacetate and then release it slowly into the reaction medium containing baker's yeast. Such biotransformations are known to produce undesired configuration of the chiral targets, especially because of the presence of certain yeast enzymes which can lead to undesirable side reactions. Use of such slow release biocatalytic system for yeast catalysed reduction of ethyl - 4 - chloroacetate, was reported to be favourable for preparing the chiral intermediate ethyl, (5) - 4 - chloro - 3 - hydroxybutyric acid. Having prepared the aforesaid synthon, further aspect in synthesis of a statin drug like atorvastatin [Brower, P.L. et.al., Tetrahedron Lett. Vol. 33, p. 2279, (1992); Bakmann, K. L. et.al. , Tetrahedron Lett., p. 2283, (1992)] mainly deals with synthesis of the chiral side chain (4R -cis)- 1,1- dimethylethyl - 6 - cyanomethyl - 2,2 - dimethyl - 1,3 - dioxane - 4 - acetate . Known chemo-enzymatic methods for preparation of key synthons have several limitations with regard to scale-up efficiency, cost effectiveness and there is a need for a simple synthetic process employing readily available starting material, for preparation of the key chiral intermediates in the synthesis of statins. Object of the Invention It is an object of this invention to provide a process for preparation of chiral intermediates (R) - 4 - cyano - 3 - hydroxybutanoate esters, hereafter referred as "chiral synthones in statin synthesis". 5 Another object of this invention is to provide a process for preparation of chiral synthones in statin synthesis by using a readily available starting material i.e. glucono delta lactone. Still another object of this invention is to provide a process for preparation of chiral synthones in statin synthesis wherein glucono delta lactone molecule, the starting material, itself provides the necessary chirality of the target compound. Yet another object of this invention is to provide a process for preparation of chiral synthones in statin synthesis which does not involve building up of any chiral centers by using chiral reagents or chiral transformation for achieving required chirality in the target molecule. Yet another object of this invention is to provide a process for preparation of chiral synthones in statin synthesis, which does not use any enzymatic process and hence is simple and cost-effective. Summary of the Invention In accordance with this invention there is provided a process for preparation of chiral synthones of formula VI as a starting material, comprising the following steps Wherein, R is a CV4 alkyl group. VI for statin synthesis using Glucono delta lactone (Formula I) step a Oxidising Glucono delta lactone with an oxidizing agent in the presence of a first catalyst to obtain an oxidized species followed by treating said oxidized species with a metal hydroxide in a first solvent to obtain a metal salt of formula II; Wherein, M is a metal atom of alkali or alkaline earth group such as Sodium, Potassium Calcium, Barium, Magnesium, step b Treating a compound of formula II with an inorganic acid of Formula : HX Wherein X is independently CI, -Br, -I, -R" - S03, wherein R" is C|. C 4 alkyl, C\. C 4 aryl, para-toluene sulphonyloxy, methane- sulphonyloxy. -R"'4©N wherein R'" is C|. C 4 alkyl, benzyl in the presence of a first organic acid medium, followed by addition of a first alcohol to obtain a compound of Formula III; step c Treating a compound of Formula III with a second alcohol of formula R - OH in presence of a second catalyst to obtain a compound of Formula IV; 7 step d Treating a compound of Formula IV with a second organic acid in the presence of a third catalyst, in a second solvent along with a salt of an organic acid to afford the compound of Formula V; and step e Treating a compound of Formula V with a compound of formula VII— R'CN VII wherein R' is tetraalkyl ammonium, silver, copper (I), copper (II), an alkali metal, an alkaline earth metal in a third solvent to obtain a compound of formula VI. Typically, the oxidizing agent is at least one oxidizing agent selected from a group of oxidizing agents consisting of hydrogen peroxide, oxygen and air. Typically, the first catalyst is at least one metal salt selected from a group of metal salts consisting of Copper sulphate, Ferric sulfate and Barium acetate. Typically, the first solvent is at least one solvent selected from a group of aqueous alcoholic solvents consisting of aqueous methyl alcohol, aqueous ethyl alcohol, aqueous propyl alcohol and aqueous isopropyl alcohol, methyl alcohol, ethyl alcohol and n-propyl alcohol. 8 Typically, the metal hydroxide is a alkaline metal hydroxide. Typically, the alkaline metal hydroxide is selected from a group of alkaline metal hydroxides consisting of sodium hydroxide and potassium hydroxide. Alternatively, the metal hydroxide is an alkaline earth metal hydroxide. Alternatively, the alkaline earth metal hydroxide is selected from a group of alkaline earth metal hydroxides consisting of calcium hydroxide, barium hydroxide and magnesium hydroxide . Typically, the compound of Formula 11 is selected from a group of compounds consisting of Sodium -D-erythronate ,Potassium -D- erythronate and calcium -D-erythronate. Typically, the first organic acid is selected from a group of organic acids consisting of acetic acid, propionic acid, and butanoic acid. Typically, the inorganic acid is selected from a group of inorganic acids consisting of Hydrobromic acid, methane sulfonic acid , p-toluenesulphonic acid , hydrochloric acid and hydroiodic acid. Typically, the first alcohol is selected from a group of alcohols consisting of methanol , ethanol and n-propanol. Typically, a compound of formula III is selected from a group of compounds consisting of 2,4-dimethanesulphonyloxy-3-hydroxybutyric acid; 2,4-diparatoluenesulphonyloxy-3-hydroxybutyric acid and 2,4-dibromo-3-hydroxybutyric acid. Typically, the second alcohol is selected from a group of alcohols consisting of methanol, ethanol and propanol. 9 Typically, the second catalyst is selected from a group of acids consisting of hydrobromic acid, methane sulphonic acid and p-toluenesulphonic acid. Typically, a compound of formula IV is selected from the group consisting of: Methyl,2,4-dimethanesulphonyloxy-3-hydroxybutyric acid, Ethyl,2,4-dimethanesulphonyloxy-3-hydroxybutyric acid, Propyl,2,4-dimethanesulphonyloxy-3-hydroxybutyric acid, Butyl,2,4-dimethanesulphonyloxy-3-hydroxybutyric acid, Methyl,2,4-diparatoluene sulphonyloxy-3-hydroxybutyric acid, Ethyl,2,4-diparatoluene sulphonyloxy-3-hydroxybutyric acid, Propyl,2,4-diparatoluene sulphonyloxy-3-hydroxybutyric acid, Butyl,2,4-diparatoluene sulphonyloxy-3-hydroxybutyric acid, Methyl,2,4-dibromo-3-hydroxybutyric acid, Ethyl,2,4-dibromo-3-hydroxybutyric acid, Propyl,2,4-dibromo-3-hydroxybutyric acid and Butyl,2,4-dibromo-3-hydroxybutyricacid. Typically, the third catalyst is a metal-carbon catalyst selected from a group of catalysts consisting of palladium - carbon and platinum carbon. Alternatively, the third catalyst is a metal selected from a group of metals consisting of zinc and iron. Typically, the second organic acid is selected from the group of organic acids consisting of acetic acid, formic acid and propionic acid. Typically, the second solvent is either an ester or ether selected from a group of solvents consisting of methyl acetate, ethyl acetate propyl acetate, diethyl ether, diisopropyl ether, methyl tert-butyl ether and dibutyl ether. Typically, the salt of an organic acid is selected from a group of organic acid salts consisting of potassium acetate, sodium acetate, calcium acetate and sodium propionate. 10 Typically, the compound of formula V is selected from a group of compounds consisting of: Methyl,4-methanesulphonyloxy-3-hydroxy butyric acid Ethyl, 4-methanesulphonyloxy-3-hydroxy butyric acid Propyl,4-methanesulphonyloxy-3-hydroxy butyric acid Butyl, 4-methanesulphonyloxy-3-hydroxy butyric acid Methyl,4-paratoluenesulphonyloxy-3-hydroxybutyric acid Ethyl,4-paratoluenesulphonyloxy-3-hydroxybutyricacid Propyl,4-paratoluenesuIphonyIoxy-3-hydroxybutyric acid Butyl,4-paratoluenesulphonyloxy-3-hydroxybutyric acid Methyl,4-bromo-3-hydroxy butyric acid Ethyl,4-bromo-3-hydroxy butyric acid Propyl,4-bromo-3-hydroxy butyric acid Butyl,4-bromo-3-hydroxy butyric acid. methyl,4-bromo-3-hydroxy butyric acid and ethyl,4-bromo-3-hydroxy butyric acid. Typically, the third solvent is at least one solvent selected from a group of solvents consisting of methanol, ethanol, propanol, isopropanol, butanol DMF , DMSO and water. Typically, the compound of Formula A is at least one compound selected from the group of compounds consisting of silver cyanide, copper (I) cyanide, copper (II) cyanide, tetraalkyl ammonium cyanide, potassium cyanide and sodium cyanide 11 SCHME -1 Preparation of Alkyl-(R)-4-cvano-3-hydroxybutanoate Wherein, M : Alkali metal, Alkaline earth metal and R : Alkyl Group (C| to C4) 12 DETAILED DESCRIPTION OF THE INVENTION: The invented process provides a new method for synthesizing an important chiral building block viz. alkyl (R) - 4 - cyano -3- hydroxybutanoate for preparation of certain statin drugs which are inhibitors of HMG - CoA Reductase. These chiral synthones are prepared by a significantly new methodology using a relatively inexpensive and easily available raw material Glucono delta lactone. Described herein below is the process for the preparation chiral synthones useful for statin synthesis in stepwise manner. Step a Glucono delta lactone is oxidized with an oxidizing agent in the presence of a first catalyst to obtain an oxidized species followed by treating said oxidized species with a metal hydroxide in a first solvent to obtain a metal salt of formula II; Wherein, M is a metal atom of alkali or alkaline earth group such as Sodium, Potassium Calcium, Barium, Magnesium. The starting material, Glucono delta lactone, Formula I is first oxidized with an oxidizing agent, typically hydrogen peroxide (30%), in the presence of first catalysts such as, metal salts, ferric sulphate, barium acetate, copper sulphate in dematerialized water at a temperature range of 20° to 60 degrees C. Preferably, temperature is maintained in the range of 48 to 50 °C. 13 This solution is stirred for 8 Hours and then tested for peroxide. It gives negative results for peroxides. Active Carbon lgm is then added to this solution and it is further concentrated. This concentrated solution is labeled as Solution A. Alternatively, oxygen and hot air can also be used as oxidizing agents. A metal hydroxide (Hydroxide of a metal from Group 1A & IIA ) , for example, sodium hydroxide is dissolved in a first solvent, typically methyl alcohol to from an alcoholic solution of the metal hydroxide. Typically, metal hydroxide selected from a group of lithium hydroxide, sodium hydroxide potassium hydroxide calcium hydroxide, strontium hydroxide, barium hydroxide and magnesium hydroxide is used. Typically, the first solvent is at least one solvent selected from a group of, methyl alcohol, ethyl alcohol, propyl alcohol, isopropyl alcohol and water. Solution A is then added to the metal hydroxide solution in a drop-wise manner over period of time, typically 8 hours. Oxygen is purged through the solution during this addition. Throughout the addition process, methanol is added to the reaction mixture to make up for the loss through evaporation. Completion of the reaction is checked using TLC. The solid obtained is then dissolved in minimum quantity of water and Calcium chloride solution (50%) is added in 30 minutes to this solution which is further concentrated at 50 °C under vacuum. Methanol is added till the solution becomes hazy and the reaction mixture is stirred at room temperature for 24 hours. Compound of Formula II is obtained as a solid and is washed at least twice with methanol and is dried at 60 °C. The oxidation reaction is carried out in the acidic, neutral and alkaline medium.' 14 Step b Treating a compound of formula II with an inorganic acid of Formula : HX Wherein X is independently, -CI, -Br, -I, -R" - S03, wherein R" is C\. C 4 alkyl, Cj. C 4 aryl, para-toluene sulphonyloxy, methane- sulphonyloxy. -R"'4©N wherein R"' is Ci. C 4 alkyl, benzyl in presence of a first organic acid medium, Followed by addition of an alcohol to obtain a compound of Formula III; Compound of Formula H selected from a group of Sodium -D-erythronate, Potassium -D-erythronate, Calcium-D erythronate is treated with an inorganic acid, typically hydrobromic acid in a first organic acid , typically acetic acid in the concentration range of 25% to 50% and the reaction mass is stirred for 20 hours at room temperature. Typically the first organic acid selected from a group acetic acid, propionic acid, and butanoic acid is used. Typically, the inorganic acid selected from a group of methane sulfonic acid , p-toluenesulphonic acid , hydrochloric acid and hydroiodic acid is used. Typically, hydrobromic acid in acetic acid in the concentration range of 30% to 34% is used. Dry alcohol typically, methanol or ethanol or propanol is then added to the reaction mixture. Addition of dry alcohol leads to an exothermic reaction and alcohol starts boiling. Alternatively, dry propanol can also be used. After completion of the reaction, the reaction mass is heated and refluxed for 3 hours. 15 Step c Treating a compound of Formula III with a second alcohol of formula R - OH in the presence of a second catalyst as acid to obtain a compound of Formula IV; Compound of formula III selected from a group of compounds consisting of 2,4- dimethanesulphonyIoxy-3-hydroxybutyric acid; 2,4-diparatoluenesulphonyloxy-3- hydroxybutyric acid and 2,4-dibromo-3-hydroxybutyric acid is used in this step. Typically, second alcohol selected from a group of alcohols consisting of methanol, ethanol and propanol is employed. Typically, the second catalyst as an acid is at least one acid selected from a group of acids consisting of hydrobromic acid, methane sulphonic acid and p-toluenesulphonic acid is used for this step. Step d Treating a compound of Formula IV with a second organic acid in presence of a third catalyst, in a second solvent along with a salt of an organic acid; and Compound of formula IV is selected from the group consisting of: Methyl,2,4-dimethanesulphonyloxy-3-hydroxybutyric acid, EthyI,2,4-dimethanesulphonyloxy-3-hydroxybutyric acid, 16 Propyl,2,4-dimethanesulphonyloxy-3-hydroxybutyric acid, Butyl,2,4-dimethanesulphonyloxy-3-hydroxybutyric acid, Methyl,2,4-diparatoluene sulphonyloxy-3-hydroxybutyric acid, Ethyl,2,4-diparatoluene sulphonyIoxy-3-hydroxybutyric acid, Propyl,2,4-diparatoluene sulphonyloxy-3-hydroxybutyric acid, Butyl,2,4-diparatoluene sulphonyloxy-3-hydroxybutyric acid, Methyl,2,4-dibromo-3-hydroxybutyricacid, Ethyl,2,4-dibromo-3-hydroxybutyric acid, Propyl,2,4-dibromo-3-hydroxybutyric acid and Butyl,2,4-dibromo-3-hydroxybutyric acid. Compound of formula is dissolved in a solvent like ester or ether along with a second organic acid like, acetic acid. Weak salt like sodium acetate and a second catalyst like palladium on carbon are added to the reaction mixture. The reaction mixture is then transferred to an autoclave. The autoclave is first purged with Nitrogen and hydrogen is introduced and the reaction mixture is stirred continuously at a temperature range of 10 to 50°C, typically in the range of 25° to 38°C. After the consumption of 1 mole of Hydrogen, the catalyst is filtered off and is washed with the ester or ether solvent. The organic layer is washed with Aqueous Sodium bicarbonate and it is dried over sodium sulfate. The filtrate is concentrated under vacuum to afford the compound of formula V. Typically, the second Organic acid selected from a group of organic acids consisting of propionic acid, butyric acid is used. Typically, an ester is used as a solvent. Typically, alkyl ester selected from a group of alkyl ester consisting of methyl acetate, ethyl acetate, propyl acetate and butyl acetate is employed. Alternatively, an ether solvent selected from a group of ether solvents diethyl ether, diisopropyl ether, methyl tert-butyl ether and dibutyl ether is used. 17 Typically, weak salt selected from a group of weak salts consisting of sodium acetate, potassium acetate and calcium acetate is used. Typically, the third catalyst is at least one catalyst selected from a group of catalysts consisting of palladium-carbon, platinum-carbon is used. Alternatively, the third catalyst is at least one catalyst selected from a group of metals like zinc and iron is used. Step e Treating a compound of Formula V with a compound of formula VII— R'CN VII wherein R' is tetraalkyl ammonium, silver, copper (I), copper (II), an alkali metal, an alkaline earth metal, in a third solvent to obtain a compound of Formula VI Wherein, R is a C 1.4 alkyl group. VI Compound of Formula V is for this step is selected from a group of compounds consisting of Methyl,4-methanesulphonyloxy-3-hydroxy butyric acid Ethyl, 4-methanesulphonyloxy-3-hydroxy butyric acid Propyl,4-rhethanesulphonyloxy-3-hydroxy butyric acid Butyl, 4-methanesulphonyloxy-3-hydroxy butyric acid Methyl,4-paratoluenesulphonyloxy-3-hydroxybutyric acid Ethyl,4-paratoluenesulphonyloxy-3-hydroxybutyric acid Propyl,4-paratoluenesulphonyloxy-3-hydroxybutyric acid 18 Butyl,4-paratoluenesulphonyloxy-3-hydroxybutyricacid Methyl,4-bromo-3-hydroxy butyric acid Ethyl,4-bromo-3-hydroxy butyric acid Propyl,4-bromo-3-hydroxy butyric acid and Butyl,4-bromo-3-hydroxy butyric acid. Compound of formula VII like sodium cynide is dissolved in demineralised water by stirring. Compound of formula V and a third solvent, typically an alcohol like isopropanol are added to the solution of Formula VII at the temperature range of 6°C to the reflux temperature of the solvent. Typically, at least one solvent selected from a group of solvents consisting of methanol, ethanol, propanol, isopropanol, butanol DMF , DMSO and water is used. The final product is checked with TLC [Solvent System: Hexane: Ethyl acetate, 6:4]. Ethyl acetate is then added to the reaction mixture and contents are stirred for 30 minutes. Aqueous layer is extracted with ethyl acetate and the extract is combined with the organic layer. The combined organic layer is then washed with saturated sodium bicarbonate. The organic layer is then dried over un-hydrous sodium sulfate and concentrated under vacuum to afford the compound of formula VI as reddish color liquid which is further distilled at 118 to 123 °C under 1 to 2 mm of vacuum to get the final product with more than 98% purity. The present invention is illustrated by the following examples, which provide particular methods for preparing compounds as per the process described in the invention. However, the examples described herein should not be considered as limiting the scope of the present invention in any way. Examples : Example 1 Calcium erythronate from Glucono-delta-lactone 19 Method -1 In a three necked flask, Glucono-delta-lactone 46 gms (0.258 mole), alongwith a mixture of ferric sulphate (0.5 gm), barium acetate(0.5 gm), copper sulphate(25 mg) was dissolved in 250 ml DM water. Temperature of the reaction mass was raised to 48 - 50°C. 30%hydr,ogen .peroxide 53 ml (0.51 mole) was added in 2 hours to the reaction mixture and it was stirred at 48 - 50°C for 8 hours until peroxide test was negative. Active carbon(lgm) was added and the reaction mixture was stirred for 30 minutes and then it was filtered. Filtrate thus obtained was concentrated under vacuum at 48 - 50°C till total volume of the mass remained approximately 150 ml. This concentrated filtrate was then kept aside as solution A. In a flask, potassium hydroxide (35gms) was dissolved in methanol (110 ml) and the resulting solution was cooled to room temp. Solution A was then added slowly in the methanolic solution in 8 hours. Simultaneously, oxygen gas was purged from 3 glass tubings under stirring for 48 hrs. The completion of oxidation was checked by by TLC. During the purging of oxygen, level of methanol was maintained by adding methanol against its loss due to evaporation. The solid obtained from the above step was then dissolved in minimum quantity of water. 50% solution of calcium chloride(30ml) was then added slowly in 30 minutes and the resulting reaction mixture was concentrated to about 150 ml at 50°C under vacuum. Methanol 120 ml was added till solution became hazy, the reaction mixture was then stirred at room temperature for 24 hrs. White solid obtained was filtered, washed with 5 ml x 2 methanol. The solid was dried at 60°C under vacuum till dryness to give 30 gms calcium erythronate . Method - 2 In three necked flask, Glucono-delta-lactone (23 gms 0.129 mole), ferric sulphate(0.25 gm), barium acetate(0.25 gm), copper sulphate(12mg) were dissolved in DM water(250 ml). 20 Temperature of the reaction mass raised to 48 - 50°C. 30% hydrogen peroxide(53 ml ,0.51 mole) was then added to the flask in 2 hrs followed by continuous stirring at 48 - 50°C for 8 hrs. Reaction contents in the flask were then tested for peroxide. There was no peroxide present and the peroxide test showed negative results. Active carbon (1 gm) was then added followed by stirring for 30 minutes. The reaction mixture was then filtered and the filtrate was concentrated under vacuum at 48 - 50°C till total volume of the filtrate was reduced to 150 ml. This concentrated filtrate was then kept aside as solution A. In another flask potassium hydroxide (35 gms) was dissolved in methanol(l 10ml), and the solution was cooled to room temp. Solution A was then slowly added to the methanolic solution in 24 hrs under stirring. Simultaneously oxygen was purged from the flask. The completion of oxidation was checked by TLC. During the purging of oxygen level of methanol was maintained by addition of methanol against its loss due to evaporation. The solid obtained was then dissolved in minimum quantity of water. 50% solution of calcium chloride (30 ml) was slowly added in 30 minutes and the resulting reaction mixture was concentrated to about 150 ml at 50°C under vacuum. Methanol (120 ml) was added till solution became hazy, the reaction mixture was then stirred at room temperature for 24 hrs. The reaction mixture was then filtered to obtain a white product which was washed with 5 ml x 2 methanol. The washed product was then dried at 60°C under vacuum . The final yield of calcium erythronate was 13 gms after complete drying . EXAMPLE-2 Preparation of Methyl-2,4-dibromo-2,4-dideoxy-threonate Method - 1 In a 500 ml glass flask equipped with a stirrer, thermometer, condenser and addition funnel 150ml, 32% HBr was added slowly to Calcium erythronate (Example - 1) 30 gms (0.17 mmol) at room temperature. Acetic anhydride (9 ml) was added to the reaction mass. The reaction mass was then stirred at RT for 20 hours. Dry methanol(300 ml) was charged slowly through addition funnel. Because of the exothermic reaction methanol started boiling. After completion of addition 21 the reaction mass was further heated and refluxed for 3 hrs. The reaction mass was cooled to room temperature and was concentrated under vacuum. To the concentrated and cooled reaction mass, ethyl acetate(300 ml) was added while stirring for 15 minutes. Water(70 ml) and Brine(70 ml) were added to the reaction mixture. Reaction mixture was stirred again and was allowed to settle. Lower aqueous layer was extracted twice with ethyl acetate (75 ml). Combined organic layer was washed with saturated sodium carbonate(100 ml) till it was made neutral. Finally organic layer was washed with saturated brine(100 ml). The organic layer was separated and dried over sodium sulfate. Reaction mass was then concentrated under vacuum and finally degassed under high vacuum at room temperature to give 30 gms of Methyl 2,4-dibromo- 2,4-dideoxy-threonate as white crystalline solid. MSm/e : 276 FTIR : 516.9, 590.2, 682.8, 736.8, 972.1, 999.1, 1080.1, 1149.5, 1207.4, 1307.6, 1357.8, 1438.5, 1708.8, 2927.7, 2958.6, 3494.8 cm "' 13C - NMR (CDCI3) 5 - 36.5 , 38.25 , 39.5 , 52 , 67.5 , 71 Method - 2 In a 500 ml glass flask equipped with a stirrer, thermometer, condenser and addition funnel Calcium erythronate (Example - 1) 30 gms (0.17 mmol) was charged and 170 ml 32% HBr in acetic acid was added slowly at room temperature. The reaction mass was then stirred at RT for 20 hours. Dry methanol (350ml) was charged slowly through addition funnel. Because of the exothermic reaction methanol started boiling. After completion of the addition of dry methanol, the reaction mass was heated and refluxed for 2.5 hours. The reaction mixture was then cooled to room temperature and concentrated under vacuum. To the concentrated and cooled reaction mixture, ethyl acetate (300ml) was added for 15 minutes while stirring. Water(70 ml) and of Brine(70 ml) were then added to the reaction mixture. Reaction mixture was then stirred again and was allowed to settle. Lower aqueous layer was extracted twice with ethyl acetate(75 ml). Combined organic layer was washed with saturated sodium carbonate(100 ml) till it became neutral. Finally organic layer was washed with saturated brine(100 ml). The organic layer was then dried over sodium sulfate. 22 The Reaction mass was then concentrated under vacuum and finally degasssed under high vacuum at room temperature to give 32 gms of Methyl 2,4-dibromo-2,4-dideoxy-threonate as white crystalline solid. MSm/e : 276 FTIR : 516.9,590.2,682.8,736.8,972.1,999.1, 1080.1, 1149.5, 1207.4, 1307.6, 1357.8, 1438.5, 1708.8, 2927.7, 2958.6, 3494.8 cm "' l3C - NMR (CDC13) 5 - 36.5 , 38.25 , 39.5 , 52 , 67.5 , 71 Preparation of Ethyl-2,4-dibromo-2,4-dideoxy-threonate Method - 3 Calcium erythronate (Example - 1) 30 gms (0.17 mmol) was added in a 500 ml glass flask equipped with a stirrer, thermometer, condenser and addition funnel, charged and slowly 170 ml 32% HBr in acetic acid was then added to the flask under stirring at room temperature for 20 hours. Dry ethanol (350 ml) was charged slowly through addition funnel. Because of the exothermic reaction methanol started boiling. After completion of addition, the reaction mixture was heated and refluxed for 2.5 hrs. The reaction mixture was then cooled to room temperature and was concentrated under vacuum. To the concentrated and cooled reaction mixture, ethyl acetate(300 ml) was added while stirring for 15 minutes. Water (70 ml) and of Brine(70 ml) were added to the reaction mixture The reaction mixture was stirred again and was allowed to settle. Lower aqueous layer was extracted twice with ethyl acetate(75 ml). Combined organic layer was washed with saturated sodium carbonate (100 ml) till it became neutral. Finally organic layer was washed with saturated brine (100 ml). The organic layer was then separated and dried over sodium sulfate. Reaction mass was then concentrated under vacuum and finally degassed under high vacuum at room temperature to give 33 gms of Ethyl 2,4-dibromo-2,4-dideoxy-threonate as white crystalline solid Preparation of n-propyl-2,4-dibromo-2,4-dideoxy-threonate 23 Method - 4 Calcium erythronate (Example - 1) 30 gms (0.17 mmol) was added in a 500 ml glass flask equipped with a stirrer, thermometer, condenser and addition funnel, charged and slowly170 ml 32% HBr in acetic acid was then added to the flask under stirring at room temperature for 20 hours. Dry n-propanol (300 ml) was charged slowly through addition funnel. Because of the exothermic reaction methanol started boiling. After completion of addition, the reaction mixture was heated and refluxed for 2.5 hrs. The reaction mixture was then cooled to room temperature and was concentrated under vacuum. To the concentrated and cooled reaction mixture, ethyl acetate(300 ml) was added while stirring for 15 minutes. Water (70 ml) and of Brine(70 ml) were added to the reaction mixture The reaction mixture was stirred again and was allowed to settle. Lower aqueous layer was extracted twice with ethyl acetate(75 ml). Combined organic layer was washed with saturated sodium carbonate (100 ml) till it became neutral. Finally organic layer was washed with saturated brine (100 ml). The organic layer was then separated and dried over sodium sulfate. Reaction mass was then concentrated under vacuum and finally degassed under high vacuum at room temperature to give 28 gms of n-propyl-2,4-dibromo-2,4-dideoxy-threonate. EXAMPLE-3 Preparation of Methyl-S-4-bromo-3-hydroxy butanoate Method - 1 Methyl - 2,4 dibromo -2,4-dideoxy threonate, 90 gms (0.32 mole) was dissolved in of ethyl acetate(720 ml) and acetic acid(90 ml) in a conical flask. This solution along with a mixtue of Sodium acetate (anhydrous), 90 gms, 5% Pd/C, 8 gms was transferred to an autoclave. The autoclave was closed and connected with water and gas supply. The autoclave was first flushed with Nitrogen (5 kgs/cm2). After evacuating Nitrogen, Hydrogen(6 kgs/cm2 )was introduced with simultaneous stirring. While Stirring, the consumption of H2 was monitored. After the consumption of 1 Molar equivalent of hydrogen, the catalyst was filtered off, and was washed with 50 ml ethyl acetate. The organic layer was washed with aq. Sodium bicarbonate and dried over anhydrous sodium sulfate. The filtrate was 24 concentrated under vacuum to give 54 gms methyl-S-4 - bromo -3 -hydroxy butanoate as liquid product.. A small sample of this liquid product was purified by distillation. FTIR : 671.2, 1049.2, 1180.4, 1296.1, 1369.4, 1438.8, 1732.0, 2360.7, 2954.7/3448.5, MSm/e : 197 l3C-NMR : 33.5,49,53.25,71,169.5 Preparation of Methyl-S-4-bromo-3-hydroxy butanoate Method - 2 Methyl - 2,4 dibromo -2,4-dideoxy threonate, 90 gms (0.32 mole) was dissolved in of ethyl acetate(720 ml) and acetic acid(90 ml) in a conical flask. This solution along with a mixtue of Sodium acetate (anhydrous), 90 gms, 5% Pd/C, 5.5 gms was transferred to an autoclave. The autoclave was closed and connected with water and gas supply. The autoclave was first flushed with Nitrogen (5 kgs/cm2). After evacuating Nitrogen, Hydrogen(6 kgs/cm2 )was introduced with simultaneous stirring. While Stirring, the consumption of H2 was monitored. After the consumption of 1 Molar equivalent of hydrogen, the catalyst was filtered off, and was washed with 50 ml ethyl acetate. The organic layer was washed with aq. Sodium bicarbonate and dried over anhydrous sodium sulfate. The filtrate was concentrated under vacuum to give 52 gms methyl-S-4 - bromo -3 -hydroxy butanoate as liquid product. A small sample of this liquid product was purified by distillation. FTIR : 671.2, 1049.2, 1180.4, 1296.1, 1369.4, 1438.8, 1732.0, 2360.7, 2954.7, 3448.5, MSm/e : 197 l3C-NMR : 33.5,49,53.25,71,169.5 Preparation of Ethyl-S-4-bromo-3-hydroxy butanoate Method : 3 Ethyl - 2,4 dibromo -2,4-dideoxy threonate, 95 gms (0.326 mole) was dissolved in of ethyl acetate(720 ml) and acetic acid(90 ml) in a conical flask. This solution was then transferred to an autoclave. Sodium acetate (anhydrous), 90 gms and 5% Pd/C, 8 gms were further added the auto clave. The autoclave was closed and connected with water and gas supply. After flushing the autoclave with Nitrogen (5 kgs/cm2) twice, Hydrogen was introducecd (6 kgs/cm2) followed by stirring. Consumption of Hydrogen was monitored and after the consumption of 1 M 25 Hydrogen the catalyst was filtered off, and the reaction mass was washed with ethyl acetate(50 ml). The organic layer was washed with aqueous Sodium bicarbonate and was dried over anhydrous sodium sulfate. The filtrate was concentrated under vacuum to give 54 gms ethyl-S-4 - bromo -3 -hydroxy butanoate as liquid product. This product was used without further purification. A small sample was purified by distillation. FTIR : 671.2, 1026.1, 1188.1, 1299.9, 1373.2, 1732.0, 2360.7, 2981.7, 3448.5 Preparation of Methyl-S-4-bromo-3-hydroxy butanoate Method - 4 In a two neck round bottom flask, Zinc powder(1.3) gms and 1.2 ml acetic acid were mixed, followed by addition of 10 ml isopropyl ether. The reaction mixture was warmed to 40°C and stirred for 15 minutes. Methyl-2,4-dibromo-2,4-dideoxy threonate (2.6 gms, 9.5 mmol) was taken in 10 ml isopropyl ether and added drop wise to the clear reaction mixture which became hazy after 2 hrs. After that isopropyl ether(40 ml) was added to the reaction mass followed by saturated ammonium chloride solution(10 ml). Then the layers were separated. Organic layer was washed with 10 ml brine and dried over sodium sulphate and was concentrated under vacuum to give 0.8 gm of the Methyl-S-4-bromo-3-hydroxy butanoate as oil. Preparation of Methyl-S-4-bromo-3-hydroxy butanoate Method - 5 Zinc powder (10.9 gms) was mixed with Glacial acetic acid, 9.6 ml in a round bottom flask fitted with a stirrer, condenser, thermometer and guard tube followed by the addition of Diethyl ether(30 ml). The reaction mass was warmed to 40°C for 15 minutes under stirring. Then Methyl - 2,4 dibromo -2,4-dideoxy threonate(38.7 gms, 0.140 mmol) in 70 ml diethyl ether was added drop wise at room temperature to the reaction mass in the flask. The reaction mass started boiling. On completion of the addition of dibromo ester, the reaction mass was stirred at room temperature for 1 hr and then refluxed for 1 hr. The mass was then cooled to 10°C and quenched with 70 ml 1 N hydrochloric acid followed by Stirring for 30 26 minutes to form a clear solution. The reaction mass was then extracted with ethyl acetate(500 ml), followed by a rewash with ethyl acetate(200 ml). The combined organic layer was washed with 3 x 70 ml saturated sodium bi carbonate solution followed by 2 x 70 ml brine. Organic layer was then dried over sodium sulfate and concentrated under vacuum to give 16.3 gms of Methyl-S-4-bromo-3-hydroxy butanoate. EXAMPLE - 4 Preparation of Methyl-R-4-cyano-3-hydroxy butanoate Method - 1 Sodium cyanide 14.1 gms (0.228 mol) was dissolved in demineralized water(255 ml ) followed by stirring for lo minutes. MethyI-S-4-bromo-3-hydroxy butanoate, 45 gms (0.228 mol) and of Isopropanol (51 ml) was added to the reaction mass at room temperature. The reaction mass was then stirred for 4 hrs. TLC was checked [System Hexane : Ethyl acetate, 6 : 4]. Ethyl acetate, 400 ml was added and stirred for 30 minutes. Aq. layer was extracted with 200 ml ethyl acetate and the combined organic layer was washed with saturated sodium bicarbonate solution. Organic layer was the dried over anhydrous sodium sulfate and concentrated under vacuum at 50 - 55°C and degassed at 50 °C under high vacuum to give 27 gms of Methyl-R-4-cyano-3- hydroxy butanoate as reddish colour liquid. Which is distilled at 118 - 123°C under 1 to 2 mm of vacuum to obtain 22 gms of the product with >98% purity. MSm/e : 143 'H-NMRofMCHB(cdcl3): (CDC13) δ 2.62 (4H,m), 3.68 (3H,s), 3.91 (lH,brs), 4.32 (lH,m), Method : 2 Preparation of Ethyl-R-4-cyano-3-hydroxy butanoate Sodium cyanide 14.1 gms (0.228 mol) was carefully dissolved by stirring for 10 minutes in demineralized water (255 ml) taken in 500 ml three neck RBF. Ethyl-S-4-bromo-3-hydroxy butanoate, 48 gms (0.228 mol) and 51 ml of Isopropanol were added to the reaction mass at room temperature. The contents were then stirred for 4 hrs. Complettion of the reaction was checked by TLC [System Hexane : Ethyl acetate, 6:4]. On completion of the reaction Ethyl acetate (400 ml) was added and the reaction mixture was stirred for 30 minutes. After 27 allowing the contents to settle, Aqueous layer was extracted with 200 ml ethyl acetate and the combined organic layer was washed with saturated sodium bicarbonate solution. Organic layer was then dried over anhydrous sodium sulfate and concentrated under vacuum at 50 - 55°C and degassed at 50 °C under high vacuum to give 29.5 gms of Ethyl-R-4-cyano-3- hydroxy butanoate as reddish colour liquid. Upon distillation of the reddish color liquid prOduct at 125 - 126°C under 1 to 2 mm of vacuum 24 gms of the product with >98% purity was obtained. MSm/e : 157 'H -NMR : (CDC13) 5 1.29 (3H,t), 2.64 (4H,m), 3.84 (lH,bs), 4.18 (2H,quartet), 4.36(lH,quintet) Optical Rotation [a] D25 = - 33.90° (C = 1.08, chloroform) Method - 3 In a 500 ml round bottom flask, sodium cyanide (6.28 gms,0.128 mol) was carefully dissolved in water(l 14 ml) by stirring for 10 minutes. Methyl - S-4 - bromo -3- hydroxy butanoate(20 gms ,0.101 mol) and ethanol(23 ml) were further added to the round bottom flask and the contents were Stirred at room Temperature for 16 hrs . Completion of reaction was checked by TLC[System : Hexane : Ethyl acetate, 6:4] . On completion of reaction, ethyl acetate (180 ml) was added and the contents were stirred for 30 minutes. After allowing the contents to settle down, Aqueous layer was extracted with 180 ml ethyl acetate and combined organic layer was washed with saturated sodium bicarbonate solution. Organic layer was then dried over sodium sulfate and concentrated under vacuum to give 11 gms of reddish color oil as the product. Upon distillation of the product under vacuum at 118 - 123°C underl to 2 mm of vacuum, purified product 9 gms with >98% purity was obtained. Method - 4 In a 500 ml round bottom flask, dimethyl sulphoxide(120 ml), Methyl - S-4 - bromo -3-hydroxy butanoate(36.7 gms), Sodium cyanide (12.7 gms) were dissolved in 45 ml demineralised water. The reaction mixture was stirred at 65°C for two hours to give 100% 28. conversion. The reaction mixture was extracted with 100 x 2 ml ethyl acetate. The organic layer was dried over sodium sulphate. The solvent was evaporated under vacuum to give 23 gms of the product with more than 95% purity. Applications: The chiral intermediates alkyl-(R)- 4 - cyano-3-hydroxybutanoate esters can be easily utilized for synthesizing statin side chains. Various statin side chains consist of mainly dihydroxyheptanoic acid or esters thereof, which are often protected and modified suitably. An example of such a side chain can be cited as (4R -cis)- 1,1- dimethylethyl - 6 -cyanomethyl - 2,2 - dimethyl - 1,3 - dioxane - 4 - acetate, which is required for synthesize an important statin drug atorvastatin calcium. While considerable emphasis has been placed herein on the specific steps of the preferred process, it will be appreciated that many steps can be made and that many changes can be made in the preferred steps without departing from the principles of the invention. These and other changes in the preferred steps of the invention will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the invention and not as a limitation. 29 We Claim:- 1. A process for preparation of chiral synthones of formula VI, for statin synthesis using Glucono delta lactone of (Formula I) as a starting material, comprising the following steps : step a Oxidising Glucono delta lactone with an oxidizing agent in the presence of a first catalyst to obtain an oxidized species followed by treating said oxidized species with a metal hydroxide in a first solvent to obtain a metal salt of formula II; Wherein, M is a metal atom of alkali or alkaline earth group such as Sodium, Potassium Calcium, Barium or Magnesium. step b Treating the compound of formula II with an inorganic acid of Formula : HX Wherein X is independently 30 8 JAN 2007 CI, -Br, -I, -R"-S03j wherein R" is C|. C 4 alkyl, . C|. C 4 aryl, para-toluene sulphonyloxy, methane- sulphonyloxy. -R"'4©N wherein R'" is C\.C 4 alkyl, benzyl in the presence of a first organic acid medium, followed by addition of a first alcohol to obtain a compound of Formula III; step c Treating the compound of Formula III with a second alcohol of formula R - OH in the presence of a second catalyst to obtain a compound of Formula IV; Step d Treating the compound of Formula IV with a second organic acid in the presence of a third catalyst, in a second solvent along with a salt of an organic acid to afford the compound of Formula V; and 31 step e Treating the compound of Formula V with a compound of formula VII— R'CN VII wherein R' is tetraalkyl ammonium, silver, copper (I), copper (II), an alkali metal, an alkaline earth metal in a third solvent to obtain the compound of formula VI. 2. A process as claimed in claim 1, wherein the oxidizing agent is at least one oxidizing agent selected from a group of oxidizing agents consisting of hydrogen peroxide, oxygen and air. 3. A process as claimed in claim 1, wherein the first catalyst is at least one metal salt selected from a group of metal salts consisting of Copper sulphate, Ferric sulfate and Barium acetate. 4. A process as claimed in claim 1, wherein the first solvent is at least one solvent selected from a group of aqueous alcoholic solvents consisting of aqueous methyl alcohol, aqueous ethyl alcohol, aqueous propyl alcohol and aqueous isopropyl alcohol. 5. A process as claimed in claim 1, wherein the first solvent is at least one alcoholic solvent selected from a group of alcoholic solvents consisting of methyl alcohol ethyl alcohol, n-propyl alcohol and isopropylalcohol. 6. A process as claimed in claim I, wherein the metal hydroxide is at least one alkaline metal hydroxide selected from a group of alkaline metal hydroxides consisting of sodium hydroxide and potassium hydroxide. 7. A process as claimed in claim 1, wherein metal hydroxide is at least one alkaline earth metal hydroxide selected from a group of alkaline earth metal hydroxides consisting of calcium hydroxide, barium hydroxide and magnesium hydroxide . 32 8. A process as claimed in claim 1, wherein the compound of Formula II is selected from a group of compounds consisting of Sodium -D-erythronate ,Potassium -D-erythronate and calcium -D-erythronate. 9. A process as claimed in claim 1, wherein the first organic acid is at least one acid selected from a group of organic acids consisting of acetic acid, propionic acid, and butanoic acid. 10. A process according to claim 1, wherein the inorganic acid is selected from a group of inorganic acids consisting of Hydrobromic acid, methane sulfonic acid , p-toluenesulphonic acid , hydrochloric acid and hydroiodic acid. 11. A process as claimed in claim 1, wherein the first alcohol is selected from a group of alcohols consisting of methanol , ethanol and n-propanol. 12. A process as claimed in claim 1, wherein a compound of formula III is selected from a group of compounds consisting of 2,4-dimethanesulphonyloxy-3-hydroxybutyric acid; 2,4-diparatoluenesulphonyloxy-3-hydroxybutyric acid and 2,4-dibromo-3-hydroxybutyric acid. 13. A process as claimed in claim 1, wherein the second alcohol is selected from a group of alcohols consisting of methanol, ethanol and propanol. 14. A process as claimed in claim 1, wherein the second catalyst is selected from a group of acids consisting of hydrobromic acid, methane sulphonic acid and p-toluenesulphonic acid. 15. A process as claimed in claim 1, wherein wherein the compound of formula IV is selected from the group consisting of : Methyl,2,4-dimethanesulphonyloxy-3-hydroxybutyric acid, Ethyl,2,4-dimethanesulphonyloxy-3-hydroxybutyric acid, Propyl,2,4-dimethanesulphonyloxy-3-hydroxybutyric acid, 33 Butyl,2,4-dimethanesulphonyloxy-3-hydroxybutyric acid, Methyl,2,4-diparatoluene sulphonyloxy-3-hydroxybutyric acid, Ethyl,2,4-diparatoluene sulphonyloxy-3-hydroxybutyric acid, Propyl,2,4-diparatoluene sulphonyloxy-3-hydroxybutyric acid, Butyl,2,4-diparatoluene sulphonyloxy-3-hydroxybutyric acid, Methyl,2,4-dibromo-3-hydroxybutyric acid, Ethyl,2,4-dibromo-3-hydroxybutyric acid, Propyl,2,4-dibromo-3-hydroxybutyric acid and Butyl,2,4-dibromo-3-hydroxybutyric acid. 16. A process as claimed in claim 1, wherein the third catalyst is a metal-carbon catalyst. 17. A process as claimed in claim 18, wherein the metal-carbon catalyst is at least one metal-carbon catalyst selected from a group of catalysts consisting of palladium -carbon and platinum carbon. 18. A process as claimed in claim 1, wherein the third catalyst is a metal. 19. A process as claimed in claim 20, wherein the metal is at least one metal selected from a group of metals consisting of zinc and iron. 20. A process as claimed in claim 1, wherein the second organic acid is selected from the group of organic acids consisting of acetic acid, formic acid and propionic acid. 21. A process as claimed in claim 1, wherein the second solvent is either an ester or ether selected from a group of solvents consisting of methyl acetate, ethyl acetate propyl acetate, diethyl ether, diisopropyl ether, methyl tert-butyl ether and dibutyl ether. 22. A process as claimed in claim 1, wherein the salt of an organic acid is at least one salt selected from a group of organic acid salts consisting of potassium acetate, sodium acetate, calcium acetate and sodium propionate. 34 23. A process as claimed in claim 1, wherein the compound of formula V is selected from a group of compounds consisting of Methyl,4-methanesulphonyloxy-3-hydroxy butyric acid Ethyl, 4-methanesulphonyIoxy-3-hydroxy butyric acid Propyl,4-methanesulphonyloxy-3-hydroxy butyric acid Butyl, 4-methanesulphonyloxy-3-hydroxy butyric acid Methyl,4-paratoluenesulphonyloxy-3-hydroxybutyric acid Ethyl,4-paratoluenesulphonyloxy-3-hydroxybutyric acid Propyl,4-paratoluenesulphonyloxy-3-hydroxybutyric acid Butyl,4-paratoluenesulphonyloxy-3-hydroxybutyric acid Methyl,4-bromo-3-hydroxy butyric acid Ethyl,4-bromo-3-hydroxy butyric acid Propyl,4-bromo-3-hydroxy butyric acid Butyl,4-bromo-3-hydroxy butyric acid. methyl,4-bromo-3-hydroxy butyric acid and ethyI,4-bromo-3-hydroxy butyric acid. 24. A process as claimed in claim 1, wherein the third solvent is at least one solvent selected from a group of solvents consisting of methanol, ethanol, propanol, isopropanol, butanol DMF , DMSO and water. 25. A process as claimed in claim 1, wherein the compound of Formula VII is at least one compound selected from the group of compounds consisting of silver cyanide, copper (I) cyanide, copper (II) cyanide, tetraalkyl ammonium cyanide, potassium cyanide and sodium cyanide 35 ABSTRACT A process for preparation of chiral synthones of formula VI, for statin synthesis using Glucono delta lactone as a starting material. The process comprises the Oxidising Glucono delta lactone, treating the oxidized species with a metal hydroxide to obtain a metal salt, treating the metal salt with an inorganic acid and further treatment with an alcohol, a second organic acid and a cyanide compound to obtain the chiral synthone. 8 JAN 2007 FORM-2 THE PATENTS ACT, 1970 (39 of 1970) & THE PATENTS RULES, 2003 PROVISIONAL Specification (See section 10 and rule 13) PROCESS FOR PREPARING ALKYL-(R)-4-CYANO-3- HYDROXYBUTANOATE, IMPORTANT INTERMEDIATES IN THE SYNTHESIS OF ANTIHYPERLIPOPROTEINEMIC AGENTS M. J. INSTITUTE OF RESEARCH A Research Institute organized under the laws of India of 113, Jolly Maker Chambers-II, Nariman Point, Mumbai 400 021, Maharashtra, India THE FOLLOWING SPECIFICATION DESCRIBES THE INVENTION. The present invention relates to a process for preparation of Alkyl-(R)-4-cyano-3-hydroxybutanoate chiral intermediates, key substances required for side chain synthesis for statin type cholesterol reducing drugs which are inhibitors of the enzyme -HMG-CoA reductase. BACKGROUND OF THE INVENTION; Statin drugs like Atorvastatin and Rosuvastatin are completely synthetic molecules while some of the earlier statins were obtained from fermentation process or by preparing semi synthetic derivatives of such fermentation products. The synthetic statins share the chiral 3,5-dihydroxyacid side chain, which is also found in certain natural products and is essential for the pharmacological activity. Synthesis of such a chiral side chain required greater skill for its preparation. The method described here is relatively simpler and easier way to synthesize the chiral synthone which can be further extended to prepare the chiral side chain of statins. In the method described by RUFF published in Ber 1889, Vol 32, pp 3672 0 3675 and 1900, vol-30 pp 1798 - 1802, from an aldolic acid derivative of saccharide with n carbon atoms oxidized by hydrogen peroxide in presence of ferric ions to an aldose derivative with n-1 carbon atoms with poor yield. In 1934 R. C. Hockett & C. S. Hudson published in J. Amer. Chem. Soc, vol 56, pp 1632-33 and in 1950 vol 72, pp 4546 by H.W. Diehl & C. S. Hudson with ~ 35% yield of aldase derivative in 1934 to ~ 45% yield in 1950. Starting with gluconate. But isolation needs difficult purification which involves use of ion exchange resins and column chromatography. 2 Methods known in prior art include use of 4 - chloroacetoacetic acid ethyl ester as the starting raw material which needs to be reduced asymmetrically by chemical, biochemical or other such methods. The chiral 4-chloro -3- hydroxybutanoate ester is then subjected to cyanation reaction to obtain the required chiral intermediate Ethyl - (R) - 4 - cyano -3 -hydroxy butanoate. However, the yield of cyanation reaction are generally low unless specific industrial design like a variable residence time reactor are employed. Besides , this process necessitates use of asymmetric reduction techniques which could prove to be expensive. Another process for the preparation of 4-chloro -3- hydroxybutanoic acid ester (Cho,S.W.et al reports reaction of epichlorohydrin with a metal cyanide in the first stage. The yield of intermediate product 4-chloro -3-hydroxybutyronitrile can be controlled by controlling the pH of reaction medium at desired level in the range of 7.0 to 8.0, particularly between 7.3 to 7.8. Resultant 4-chloro -3- hydroxybutyronitrile, is next subjected to acid hydrosis, preferably in presence of an alcohol medium, to obtain an ester of 4-chloro -3- hydroxy butanoic acid i.e. the required product. However, as inferred from this patent document, preparation of an optically active 4-chloro -3- hydroxybutanoic acid ester will require use of chiral epichlorohydrin. This can prove to be a very expensive raw material in the process. Since synthesis of chiral key intermediates of the statin drug substances like Atorvastatin requires chiral 4-chloro -3- hydroxybutanoic acid ester, the above process is likely to turn out to be economically less feasible. Furthermore, synthesis of the cihral synthon Alkyl, -(R)- 4 -cyano - 3 - hydroxybutanoate, from chiral 4-chloro -3- hydroxybutanoic 3 acid ester arising from such a process, may also need variable residence time type specific reactor designs so a to achieve good yields. In addition to above process known in the existing art, there are also reported biochemical methods which involve chemo-enzymatic, aldolase catalysed processes for enantioselective statin intermediates, (e.g. Greenberg et al, Junjie et al, Ohrlein et al). Such enzymatic processes, in general, involve aldol type reactions, while utilizing DERA (i.e. Deoxyribose - 5 - phosphate - 5 - aldolase ). The process employ smaller building blocks of two carbons atoms like chloroacetaldehyde, acetaldhyde etc which are sequentially condensed in presence of DERA and form the six carbon lactone intermediate, Such a lactone product can then be derivatised into required chiral synthon , e.g. Alkyl - (R) - 4 - cyano - 3 -hydroxybutanoate. Some of the chemo-enzymatic processes also report use of DERA mutants which are specifically developed to enhance its capability and utility in sequential aldol condensations. These DERA mutants are reported to be performing more efficiently as compared to the wild type DERA. Advantages like higher catalytic activity, better acceptability of the substrate molecules etc., were observed by the researchers. Baker's yeast as well as several yeast strains have also been used for making the chiral synthon, 4 - chloro - 3 - hydroxybutanoate ethyl ester from ethyl - 4 - chloro acetoacetate. Certain research groups e.g. Houng et.al. Have recently applied slow release biocatalysis methods, so as to achieve asymmetric reduction of ethyl -4 - chloroacetoacetate. The process, employs Amberlite type resins which first absorb the substrate molecules i.e. 4 - chloroacetoacetate and then release it slowly into the 4 reaction medium containing baker's yeast. Such biotransformations are often known to produce undesired configuration of the chiral targets, especially due to the presence of certain yeast enzymes which can lead to undesirable side reactions. Use of such slow release biocatalytic system for yeast catalysed reduction of ethyl - 4 - chloroacetate, was reported to be favourable for preparing the chiral intermediate ethyl, (5) - 4 - chloro - 3 - hydroxybutyric acid. Nevertheless, scale-up efficiency and cost effectiveness of such chemo-enzymatic methods for preparation of key synthons for the statin drugs need to be evaluated with regard to industrial implications and commericialisation. Having prepared the aforesaid synthon, further aspect in synthesis of a statin drug like atorvastatin mainly deals with synthesis of the chiral side chain (4R -cis)- 1,1- dimethylethyl - 6 - cyanomethyl - 2,2 - dimethyl -1,3 - dioxane - 4 - acetate . The process in accordance with this invention is designed in such a way that Glucono Delta Lactone molecule itself provides the necessary chirality of the target compound. The synthetic steps worked out to develop the process are fairly simple chemical reactions and do not require building up of any chiral centers to achieve required chirality in the target molecule. The chiral intermediates Alkyl-(R)- 4 - cyano-3-hydroxybutanoate esters can be easily utilised for synthesizing statin side chains. Various statin side chains consist of mainly dihydroxyheptanoic acid or esters thereof, which are often protected and modified suitably. An example of such a side chain can be cited as (4R -cis)- 1,1- dimethylethyl - 6 - cyanomethyl - 2,2 - 5 dimethyl - 1,3 - dioxane - 4 - acetate, which is required for synthesize an important statin drug atorvastatin calcium. SCHEME-1 Preparation of Alkyl-(R)-4-cvano-3-hydroxvbutanoate M : Alkali / Alkaline earth metal R : Alkyl Group (d to C4) 6 This is followed by reducing the cyano group so as to yield the aminomethyl product viz. (4R -cis)- 1, 1 - dimethylethyl - 6 - (2 -Aminoethyl) - 2,2 - dimethyl - 1,3 - dioxane - 4 - acetate. The amino methyl chiral side chain is then condensed with a substituted diketo compound by Pall - Knorr synthesis, when a multisubstituted pyrrole derivative results. The pyrrole product is further manipulated by simple reactions like acidic deprotection, alkaline hydrolysis, and salt formation to finally yield atorvastatin calcium. SUMMARY OF INVENTION : This invention discloses a novel specific methodology for preparing the chiral intermediates (R) - 4 - cyano - 3 - hydroxybutanoate esters, which are very important in onward synthesis of chiral side chains of statins. A feature of the process in accordance with this invention is the synthesize of the required chiral molecule from relatively inexpensive and easily available raw material viz. Gluconol delta lactone. The said parent substance also serves as a chiral raw material in such a way that the target chiral intermediate (R) - 4 - cyano - 3 - hydroxybutanoate ester is synthesized easily, without any need of building a stereogenic center by using chiral reagents or chiral transformation. Different chemical reactions utilized in the process are relatively simpler reactions like oxidation, halogenation, dehalogenation, esterifications, cyanation and the like, which can also be scaled -up to manufacturing level. Besides, the process in accordance with this invention is also expected to be economically attractive and can eventually assist in reducing cost of statin type of drugs. In accordance with the above, a first aspect of the present invention relates to utilization of Glucono delta lactone, the compound of formula -1 7 HO OH I as a raw material for synthesis of the target chiral intermediates. A second aspect of the present invention deals with an improved process for the preparation of compounds of formula VI, Where R is an alkyl group of one to four carbon atoms. Which comprises the steps of: (a) treating a compound of formula V Where R is an alkyl group of one to four carbon atoms and X is a leaving group Such as, for example a halogen, R" - S03 - wherein R" is alkyl of from one carbon atoms to four carbon atoms or aryl such as for example, para-toluene sulphonyloxy, methane-sulphonyloxy, and the like or R'"4 © N wherein R'" is an alkyl of from one to from carbon atoms, or benzyl and the like with R' CN a compound formula - A 8 Where in R' is tetra alkyl ammonium, silver, copper (I), copper (II), an alkali metal, or an alkaline earth metal in a solvent at about 0° to about the reflux temperature of the solvent to afford a compound of formula VI, and, (b) treating a compound of formula IV Wherein R and X are as above, under controlled reaction conditions which include hydrogenation environment, with or without hydrogen pressure in presence of metal catalysts such as palladium carbon, platinum-carbon, nickel and alike or metals such as zinc, iron, tin and alike, and organic acids such as formic, acetic, propionic, butanoic or alike, as well as solvents such as organic esters of formula R - CO - O-R ethers of formula R - O - R wherein R is as above, and salts of organic acids with formula -B. R-COO-M, -B Wherein R is as above while M is a metal atom of alkali or alkaline earth group such as Sodium, Potassium Calcium, Barium, Magnesium and alike while B is derived from an organic acid of formula R-COOH where in R is as above, and a metal atom like Lithium, Sodium, Potassium, Calcium, Barium, Magnesium, Zinc and alike at temp. 15° - 60° C, so as to afford a compound of formula - V, and 9 (c) treating a compound of formula - III Wherein X is as above, with an alcohol of formula R - OH Wherein R is as above, in presence of strong acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, methane sulphonic acid, paratoluene sulphonic acid and alike, at temperatures 15°c to reflux temperature of the alcohol, so as to afford a compound of formula - IV and (d) treating a compound of formula II Wherein M is as above with a compound of formula HX wherein X is as above in presence of an organic acid medium R - COOH at a temperature range of 15°cto80°c so as to afford a compound of formula - III and (e) treating a compound of formula -1 viz. Glucono delta lactone. 10 Which is subjected to successive and sequential oxidation by using a peroxide like hydrogen peroxide, oxygen gas and or air in an alcohol alone or an aqueous alcohol with formula of alcohol as R - OH, wherein R is as above in presence of metal hydroxides like M - OH wherein M is as above, at a temperature range of 10°c to 75°c, so as to afford a compound of formula-II. Herein after, the present invention is explained in details. DETAILED DESCRIPTION OF THE INVENTION: The invented process provides a new method for synthesizing an important chiral building block viz* alkyl (R) - 4 - cyano -3- hydroxybutanoate for preparation of certain statin drugs which are inhibitors of HMG - CoA Reductase. This chiral intermediate is prepared by a significantly new methodology using a relatively inexpensive and easily available raw material Glucono delta lactone. The process adopts relatively simpler chemical reactions without need of building new chiral centers or utilizing chiral reagents. The process of present invention is new, improved and economically viable method for obtaining chiral building blocks for statins. In this description the term 'alkyl' means a straight chain hydrocarbon group of 1 to 4 carbon atoms such as methyl, ethyl and the like. Alkali or Alkaline earth metal is a metal in group 1A of the periodic table and includes, for example sodium, potassium, lithium, calcium, barium, magnesium and the like. 11 The compound of formula I is Glucono delta lactone, which is a very easily and commonly available substance used in several industrial operations. The oxidation of the molecule of Formula-I with help of hydrogen peroxide, oxygen and or air at proper temperature of 20° to 60°C preferably 30° to 42°C in a polar medium of water and primary alcohols or alcohol alone which may be methyl, ethyl, propyl, isopropyl etc, but preferably methyl or ethyl. The oxidation reaction is carried out in the acidic, neutral and alkaline medium with the help of hydroxides of group 1A of alkali metal such as lithium, sodium or potassium but preferable potassium or sodium, and alkaline earth metals like calcium, strontium, barium, magnesium etc. but preferably calcium or magnesium. The oxidation of (I) by hydrogen peroxide solution to effect oxidative decarboxylation is carried out in aqueous medium at acidic to neutral pH using catalytic agents like salts of iron, barium and copper or such metals used in oxidation processes. Such methods are reported in literature e.g. by Hockett et. al., Fletcher et. al., Wei et. al., Jacobson et. al., Isbell et. al., Walon et. al. , Tamion et. al. and the like . The decarboxylated mass, as aqueous or aqueous alcoholic solution or suspension is then oxidized sequentially under neutral to alkaline pH in presence of metal hydroxides or carbonates of alkaline or alkaline earth metals as described above and catalytic proportions of salts mentioned above to obtain a metal salt of L-threonic acid (II) e.g. calcium 1-threonate. This oxidative step is carried out by passing oxygen or air or both in the aqueous or aqueous alcoholic solution of the reaction mass. Compound of Formula III is prepared by treating a compound of Formula II with hydrobromic acid in acetic acid with certain required concentration up to 34% preferably 30 to 34%. The dibromo compound of Formula III 12 was then converted to an ester of the acid by treating it with a Cj - 4 alcohol in acidic medium , alone or with another solvent but preferably the alcoholic solvent is used alone. The 4-(halo)-3-hydroxy butanoic acid ester of Formula V where halo is preferably chloro or bromo and ester is preferably of ethyl or methyl alcohol is prepared by reacting compound of Formula IV in organic solvent preferably alkyl ester most preferably ethyl acetate in an organic acid medium, preferably acetic acid in the presence of weak salt preferably acetate of group 1A alkali metal preferably sodium or potassium. This reaction is carried out in presence of a catalyst such as platinum on carbon, 3% to 5% w/w or Palladium on carbon, 3 to 10% w/w preferably 5% w/w concentration of 2 to 6% of compound of Formula IV but preferably 3 to 4%, with hydrogen under pressure in an autoclave until 1 unit molar equivalent of hydrogen was consumed at 10 to 50°C preferably at 25° to 38°C. The worked up mass of the Formula V is wherein R is an alkyl group of 1 to 4 carbon atoms and is a leaving group with a compound of Formula . Rl-CN wherein Rl is an alkali metal or an alkaline earth metal in a polar solvent such as for example ethanol , isopropanol, DMF, DMSO and mixture thereof with water at 0°C to reflux temperature of the solvent system preferably at 40°C to afford compound of formula VI. The present invention is illustrated by the following examples, which provide particular methods for preparing compounds as per the process described in the invention. However, the examples described herein should not be considered as limiting the scope of the present invention in any way. 13 Example -1 Calcium threonate from Glucono-delta-lactone Method - 1 In a 1 lit three necked flask, charged 46 gms (0.258 mole) Glucono-delta-lactone, of 0.5 gm ferric sulphate, 0.5 gm barium acetate, 25 mg copper sulphate and 250 ml DM water. Temperature of the reaction mass raised to 48 - 50°C. Charged 53 ml (0.51 mole) of 30% hydrogen peroxide in 2 hrs. Stirred at 48 - 50°C for 8 hrs. Tested for peroxide test and found it negative. 1 gm active carbon added, stirred for 30 minutes and filtered. Filtrate concentrated under vacuum at 48 - 50°C till total volume of the mass remained app. 150 ml and kept it aside (solution A). In a 1 lit flask charged 35 gms potassium hydroxide and dissolved it in 110 ml methanol, cooled to room temp, add slowly solution A in the methanolic solution in 8 hrs also simultaneously start perging of oxygen gas from 3 glass tubings under stirring for 48 hrs . Check the completion oxidation by TLC. During the purging of oxygen level of methanol is maintained by adding methanol against its loss due to evaporation. The solid obtained is dissolved by adding minimum quantity of water. Added slowly 30 ml of 50% solution of calcium chloride in 30 minutes. The reaction mass is concentrated to about 150 ml at 50°C under vacuum. Methanol 120 ml was added till solution became hazy, the reaction mixture was then stirred at room temperature for 24 hrs. White solid obtained is filtered, washed with 5 ml x 2 methanol. The solid was dried at 60°C under vacuum till dryness to give 30 gms calcium L- threonate monohydrate. m.p. > 300°C, [a]25D + 14° 14 Method - 2 In a 1 lit three necked flask, charged 23 gms (0.129 mole) Glucono-delta- lactone, of 0.25 gm ferric sulphate, 0.25 gm barium acetate, 12 mg copper sulphate and 250 ml DM water. Temperature of the reaction mass raised to 48 - 50°C. Charged 53 ml (0.51 mole) of 30% hydrogen peroxide in 2 hrs. Stirred at 48 - 50°C for 8 hrs. Tested for peroxide test and found it negative. 1 gm active carbon added, stirred for 30 minutes and filtered. Filtrate concentrated under vacuum at 48 - 50°C till total volume of the mass remained app. 150 ml and kept it aside (solution A). In a 1 lit flask charged 35 gms potassium hydroxide and dissolved it in 110 ml methanol, cooled to room temp, add slowly solution A in the methanolic solution in 24 hrs also simultaneously start perging of oxygen gas from 3 glass tubings under stirring for 36 hrs. Check the completion oxidation by TLC. During the purging of oxygen level of methanol is maintained by adding methanol against its loss due to evaporation. The solid obtained is dissolved by adding minimum quantity of water. Added slowly 30 ml of 50% solution of calcium chloride in 30 minutes. The reaction mass is concentrated to about 150 ml at 50°C under vacuum. Methanol 120 ml was added till solution became hazy, the reaction mixture was then stirred at room temperature for 24 hrs. White solid obtained is filtered, washed with 5 ml x 2 methanol. The solid was dried at 60°C under vacuum till dryness to give 13 gms calcium L- threonate monohydrate. m.p.>300°C, [α]25D+14° 15 EXAMPLE-2 Preparation of Methyl-2,4-dibromo-3-hydroxy butanoate Method - 1 In a 500 ml glass flask equipped with a stirrer, thermometer, condenser and addition funnel Calcium L-threonate (Example - 1) 30 gms (0.17 mmol) is charged and slowly 150 ml 32% HBr in acetic acid is added at room temperature. Added 9 ml acetic anhydride to the reaction mass and stirred at RT for 20 hrs. Then 300 ml of dry methanol is charged slowly through addition funnel. Exothermic reaction, methanol started boiling. After addition the reaction mass is heated and refluxed for 3 hrs. Then it is cooled to room temperature and concentrated under vacuum. The reaction mass is then cooled to room temperature and to it added 300 ml of ethyl acetate, stirred for 15 minutes and add 70 ml of water and 70 ml of Brine. Reaction mixture is then stirred and allowed to settle. Lower aqueous layer is extracted twice with 75 ml of ethyl acetate. Combined organic layer is washed with 100 ml of saturated sodium carbonate till neutral. Finally organic layer is washed with 100 ml saturated brine. Separated the organic layer and dried over sodium sulfate. Reaction mass is then concentrated under vacuum and finally degas under high vacuum at room temperature to give 30 gms of Methyl 2,4-dibromo-3-hydroxy butanoate as light orange oil. MSm/e : 276 FTIR : 516.9,590.2,682.8,736.8,972.1,999.1, 1080.1, 1149.5, 1207.4, 1307.6, 1357.8, 1438.5, 1708.8, 2927.7, 2958.6, 3494.8 cm _I 13C - NMR (CDC13) δ - 36.5 , 38.25 , 39.5 , 52 , 67.5 , 71 16 EXAMPLE-3 Preparation of Methyl-4-bromo-3 -hydroxy butanoate Method-1 A Methyl - 2,4 dibromo -3- hydroxy butanoate, 90 gms (0.32 mole) is dissolved in 720 ml of ethyl acetate and 90 ml acetic acid in a conical flask. This solution is charged in to the autoclave. Sodium acetate (anhydrous), 90 gms and 5% Pd/C, 8 gms is also charged in the auto clave. The autoclave is closed and connected with water and gas supply. The autoclave is evacuated and then applied N2 pressure (5 kgs/cm ), again evacuated it and then H2 pressure 6 kgs/cm is taken. Stirring is started and monitored the consumption of H2. 1 Molar equivalent of hydrogen was consumed. The catalyst is filtered off, washed with 50 ml ethyl acetate. The organic layer is washed with aq. Sodium bicarbonate and dried over anhydrous sodium sulfate. The filtrate is concentrated under vac to give 54 gms methyl-4 - bromo -3 -hydroxy butanoate as liquid product. Which is used without further purification. A small sample is purified by distillation. FTIR : 671.2, 1049.2, 1180.4, 1296.1, 1369.4, 1438.8, 1732.0,2360.7, 2954.7, 3448.5, MSm/e : 197 13C-NMR : 33.5,49,53.25,71,169.5 Preparation of Ethyl-4-bromo-3 -hydroxy butanoate Method : 1 B Eethyl - 2,4 dibromo -3- hydroxy butanoate, 95 gms (0.326 mole) is dissolved in 720 ml of ethyl acetate and 90 ml acetic acid in a conical flask. 17 This solution is charged in to the autoclave. Sodium acetate (anhydrous), 90 gms and 5% Pd/C, 8 gms is also charged in the auto clave. The autoclave is closed and connected with water and gas supply. The autoclave is evacuated and then applied N2 pressure (5 kgs/cm ) evacuated it and then H2 pressure 6 kgs/cm2 is taken. Stirring is started and monitored the consumption of H2. 1 Molar equivalent hydrogen was consumed. The catalyst is filtered off, washed with 50 ml ethyl acetate. The organic layer is washed with aq. Sodium bicarbonate and dried over anhydrous sodium sulfate. The filtrate is concentrated under vacuum to give 54 gms ethyl-4 -bromo -3 -hydroxy butanoate as liquid product. Which is used without further purification. A small sample is purified by distillation. FTIR : 671.2, 1026.1, 1188.1, 1299.9, 1373.2, 1732.0, 2360.7, 2981.7, 3448.5 Method - 2 Zinc powder, 1.3 gms is charged in 100 ml two neck round bottom flask and 1.2 ml acetic acid was added to it, followed by addition of 10 ml isopropyl ether. The reaction mixture was warmed to 40°C and stirred for 15 minutes. 2.6 gms (9.5 mmol) Methy 1-2,4-dibromo-3-hydroxy butanoate was taken in 10 ml isopropyl ether and added drop wise to the clear reaction mixture which became hazy after 2 hrs. After that 40 ml isopropyl ether was added to the reaction mass followed by 10 ml of saturated ammonium chloride solution. Then layers separated. Organic layer is washed with 10 ml brine and dried over sodium sulphate and concentrated under vacuum to give 0.8 gm of the desired product as an oil. Method - 3 Zinc powder, 10.9 gms is charged in 500 ml round bottom flask fitted with a stirrer, condenser, thermometer and guard tube. Glacial acetic acid, 9.6 18 ml was added to it with 30 ml diethyl ether. The reaction mass was warmed to 40°C for 15 minutes under stirring. Then 38.7 gms (0.140 mmol) Methyl - 2,4 dibromo -3- hydroxy butanoate in 70 ml diethyl ether was added drop wise at room temperature. The reaction mass started boiling. On completion of the addition of dibromo ester, the reaction mass was stirred at room temperature for 1 hr and then refluxed for 1 hr. The mass is then cooled to 10°C and quenched with 70 ml 1 N hydrochloric acid. Stirred for 30 minutes to form clear solution. The reaction mass was extracted with 500 ml ethyl acetate, followed by 200 ml ethyl acetate. The combined organic layer was washed with 3 x 70 ml saturated sodium bi carbonate solution followed by 2 x 70 ml brine. Organic layer dried over sodium sulfate and concentrated under vacuum to give 16.3 gms of Methyl-4-bromo-3-hydroxy butanoate. EXAMPLE - 4 Preparation of Methyl-R-4-cyano-3 -hydroxy butanoate Method - 1 - A Sodium cyanide 14.1 gms (0.228 mol) is carefully taken in 500 ml three neck RBF. Demineralized water, 255 ml,is charged in the flask and stirred for 10 minutes to dissolve it. Methyl-R-4-bromo-3-hydroxy butanoate, 45 gms (0.228 mol) and 51 ml of Isopropanol is added to the reaction mass at room temperature. Stirred for 4 hrs . TLC is checked [System Hexane : Ethyl acetate, 6 : 4]. Ethyl acetate, 400 ml is added and stirred for 30 minutes. Aq. layer is extracted with 200 ml ethyl acetate and the combined organic layer is washed with saturated sodium bicarbonate solution. Organic layer dried over anhydrous sodium sulfate and concentrated under vac. at 50 - 55°C and degas at 50 °C under high vac to give 27 gms of Methyl-R-4-cyano-3-hydroxy butanoate as reddish colour liquid. Which is 19 distilled at 118 - 123°C under 1 to 2 mm of vacuum to obtained 22 gms of the product with >98% purity. MSm/e : 143 *H - NMR of MCHB (cdcl3) : (CDC13) δ 2.62 (4H,m), 3.68 (3H,s), 3.91 (lH,brs), 4.32 (lH,m), Method : 1-B Preparation of Ethyl-R-4-cyano-3 -hydroxy butanoate Sodium cyanide 14.1 gms (0.228 mol) is carefully taken in 500 ml three neck RBF. Demineralized water, 255 ml, is charged in the flask and stirred for 10 minutes to dissolve it. ethyl-R-4-bromo-3-hydroxy butanoate, 48 gms (0.228 mol) and 51 ml of Isopropanol is added to the reaction mass at room temperature. Stirred for 4 hrs. TLC is checked [System Hexane : Ethyl acetate, 6:4]. Ethyl acetate, 400 ml is added and stirred for 30 minutes. Aq. layer is extracted with 200 ml ethyl acetate and the combined organic layer is washed with saturated sodium bicarbonate solution. Organic layer dried over anhydrous sodium sulfate and concentrated under vac. at 50 - 55°C and degas at 50 °C under high vac to give 29.5 gms of Ethyl-R-4-cyano-3-hydroxy butanoate as reddish colour liquid. Which is distilled at 125 - 126°C under 1 to 2 mm of vacuum to obtained 24 gms of the product with >98% purity. MSm/e : 157 'H-NMR : (CDC13) δ 1.29 (3H,t), 2.64 (4H,m), 3.84 (lH,bs), 4.18 (2H,quartet), 4.36 (lH,quintet) Optical Rotation [α] D25 = - 33.90° (C = 1.08, chloroform) 20 Method - 2 In a 500 ml round bottom flask 114 ml of water is charged and then carefully added 6.28 gms (0.128 mol) sodium cyanide and stirred for 10 minutes to dissolve it. Added 20 gms (0.101 mol) Methyl - 4 - bromo -3-hydroxy butanoate and 23 ml ethanol. Stirred at RT for 16 hrs . TLC checked [System: Hexane : Ethyl acetate, 6:4] for the completion of reaction. On completion of reaction, added 180 ml ethyl acetate, stirred for 30 minutes and allowed to settle. Aq. Layer extracted again with 180 ml ethyl acetate and combined organic layer washed with saturated sodium bicarbonate soln. Organic layer dried over sodium sulfate and concentrated under vacuum to give 11 gms of reddish color oil as the product. Distilled under vacuum at 118 - 123°C under 1 to 2 mm of vacuum gave 9 gms with >98% purity. In accordance with this invention therefore there is provided a process, for preparation of Alkyl,(R) - 4-cyano - 3 - hydroxybutanoate esters, while employing Glucono delta lactone as a new parent material for its synthesis, said process comprising the steps of preparation of compounds of formula VI, where R is an alkyl group of one to four carbon atoms, which comprise treating a compound of formula V 21 where R is an alkyl group of one to four carbon atoms and X is a leaving group such as, for example, a halogen, R" - S03 - wherein R" is alkyl of from one carbon atoms to four carbon atoms or any other such as for example, para-toluene sulphonyloxy, methane-sulphonyloxy, and the like or R'"[email protected] wherein R'" is an alkyl of from one to four carbon atoms, or benzyl and the like; with R' CN a compound of formula -1 A where in R' is tetraalkyl ammonium, silver, copper (I), copper (II), an alkali metal, or an alkaline earth metal in a solvent at about 0° C to about the reflux temperature of the solvent to afford a compound of formula VI. In accordance with one embodiment of the invention the process for preparation of compounds of Formula V, involves treating a compound of formula IV wherein R and X are as above, under controlled reaction conditions which include hydrogenation environment, with or without hydrogen pressure in presence of metallic catalysts such as palladium-carbon, platinum-carbon, nickel and alike; or metals such as zinc, iron, tin and alike, and organic acids such as formic, acetic, propionic, butanoic or alike, as well as solvents such as organic esters of formula R - CO - O-R or ethers of formula R - O - R wherein R is as above, and salts of organic acids with formula - B. R - COO - M (B) 22 wherein R is as above while M is a metal atom of alkali or alkaline earth group such as Sodium, Potassium Calcium, Barium, Magnesium and alike at temp. 15° - 60° C, afford a compound of formula - V. In accordance with another typical embodiment of the invention the preparation of compounds of Formula IV, involves treating a compound of formula - III wherein X is as above* with an alcohol of formula R - OH wherein R is as above, in presence of strong acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, methane sulphonic acid, paratoluene sulphonic acid and alike, at temperatures 0°c to reflux temperature of the alcohol, so as to afford a compound of formula - IV . In accordance with yet another embodiment the process for preparation of compounds of Formula III, involves treating a compound of formula II wherein M is as above with a compound of formula HX wherein X is as above in presence of an organic acid medium R - COOH at a temperature range of 15°cto80°c so as to afford a compound of Formula - III. 23 In accordance with yet another embodiment the process for preparation of compounds of Formula II involves , treating a compound of formula -1 which is subjected to oxidation by using hydrogen peroxide, oxygen gas and or air in an alcohol alone or an aqueous alcohol with formula of alcohol as R - OH, wherein R is as above in presence of a metal hydroxide M - OH wherein M is as above, at a temperature range of 10°c to 75 °c, so as to afford a compound of formula - II Typically, the solvent used in the process steps disclosed is selected from the group consisting of a mixture of isopropanol - water , ethanol-water, methanol-water and butanal - water, methanol, ethanol, propanol, butanol and isopropanol. Typically, the compound of formula V is selected from the group consisting of: Methyl,4-methanesulphonyloxy-3-hydroxy butyric acid Ethyl, 4-methanesulphonyloxy-3-hydroxy butyric acid Propyl,4-methanesulphonyloxy-3-hydroxy butyric acid Butyl, 4-methanesulphonyloxy-3-hydroxy butyric acid Methyl,4-paratoluenesulphonyloxy-3-hydroxybutyric acid Ethyl,4-paratoluenesulphonyloxy-3-hydroxybutyric acid 24 Propyl,4-paratoluenesulphonyloxy-3 -hydroxybutyric acid Butyl,4-paratoluenesulphonyloxy-3 -hydroxybutyric acid Methyl,4-bromo-3-hydroxy butyric acid Ethyl,4-bromo-3-hydroxy butyric acid Propyl,4-bromo-3-hydroxy butyric acid, and Butyl,4-bromo-3-hydroxy butyric acid Typically, the compound of formula 5 is selected from the group consisting of methyl,4-bromo-3-hydroxy butyric acid; ethyl,4-bromo-3-hydroxy butyric acid; methyl,4-paratoluenesulphonyloxy-3-butyric acid and ethyl,4-paratoluenesulphonyloxy-3-hydroxy butyric acid. Typically, the compound of formula 1 is selected from the group consisting of silver cyanide, copper (I) cyanide, copper (II) cyanide, tetraalkyl ammonium cyanide, potassium cyanide or sodium cyanide. Typically, the compound of formula 1A is selected from the group consisting of potassium cyanide or sodium cyanide. Typically, the compound of formula IV is selected from the group consisting of: Methyl,2,4-dimethanesulphonyloxy-3-hydroxybutyric acid, Ethy 1,2,4-dimethanesulphonyloxy-3-hydroxybutyric acid, Propyl,2,4-dimethanesulphonyloxy-3-hydroxybutyric acid, Butyl,2,4-dimethanesulphonyloxy-3-hydroxybutyricacid, Methyl,2,4-diparatoluene sulphonyloxy-3-hydroxybutyric acid Ethyl,2,4-diparatoluene sulphonyloxy-3-hydroxybutyric acid Propyl,2,4-diparatoluene sulphonyloxy-3-hydroxybutyric acid 25 Butyl,2,4-diparatoluene sulphonyloxy-3-hydroxybutyric acid Methyl,2,4-dibromo-3-hydroxybutyricacid, Ethyl,2,4-dibromo-3-hydroxybutyric acid, Propyl,2,4-dibromo-3-hydroxybutyric acid, and Butyl,2,4-dibromo-3-hydroxybutyric acid, Typically, the metallic catalysts are selected from the group consisting of palladium - carbon , platinum carbon, zinc and iron. Typically, the organic acids are selected from the group consisting of acetic acid, formic acid , propionic acid., and butanoic acid. Typically, the ester solvents are selected from the group consisting of methyl acetate, ethyl acetate and propyl acetate. Typically, the ether solvents are selected from the group consisting of diethyl ether, diisopropyl ether, methyl tert-butyl ether and dibutyl ether. Typically, the salts of organic acids are selected from the group consisting of potassium acetate, sodium acetate, calcium acetate and sodium propionate. Typically, the compound of formula III is selected from the group consisting of 2,4-dimethanesulphonyloxy-3-hydroxybutyric acid; 2,4-diparatoluenesulphonyloxy-3-hydroxybutyric acid and 2,4-dibromo-3-hydroxybutyric acid 26 Typically, the alcohols used in the process are selected from the group consisting of methanol, ethanol and propanol. Typically, the acid catalysts used in the process are selected from the group consisting of hydrobromic acid, methane sulphonic acid and p-toluenesulphonic acid. Typically, the compound of Formula II is selected from the group consisting of Sodium-D-erythronate, potassium-D-erythronate. Typically, the acids used in the process are selected from the group consisting of hydrobromic acid, methane sulphonic acid, p-toluene sulphonic acid, hydrochloric acid and hydroiodic acid. Typically, the oxidation involved in the process steps of this invention is carried out using the reagents from the group consisting of oxygen, air or a mixture of oxygen and air. Typically, the reaction medium is selected from the group of alcohols consisting of methanol, ethanol, isopropanol and n-propanol, aqueous ethanol, aqueous methanol, aqueous propanol and aqueous isopropanol. Typically, the metal hydroxide is selected from a group consisting of sodium hydroxide, potassium hydroxide, calcium hydroxide and barium hydroxide. While considerable emphasis has been placed herein on the chemical compounds of the preferred embodiments, it will be appreciated that many permutations and combinations of the process steps can be made in the 27 preferred process steps without departing from the principles of the invention. These and other changes in the preferred process steps as well as other process steps of the invention will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the invention and not as a limitation. 28

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55-mum-2006-description(granted)-(8-1-2010).pdf

55-MUM-2006-FORM 1(13-1-2006).pdf

55-MUM-2006-FORM 1(25-8-2009).pdf

55-mum-2006-form 18(5-12-2007).pdf

55-mum-2006-form 2(25-8-2009).pdf

55-mum-2006-form 2(complete)-(8-1-2007).pdf

55-mum-2006-form 2(granted)-(8-1-2010).pdf

55-MUM-2006-FORM 2(TITLE PAGE)-(25-8-2009).pdf

55-MUM-2006-FORM 2(TITLE PAGE)-(8-1-2007).pdf

55-mum-2006-form 2(title page)-(complete)-(8-1-2007).pdf

55-mum-2006-form 2(title page)-(granted)-(8-1-2010).pdf

55-MUM-2006-FORM 3(21-10-2008).pdf

55-MUM-2006-FORM 5(8-1-2007).pdf

55-mum-2006-form-1.pdf

55-mum-2006-form-2 (complete).pdf

55-mum-2006-form-2 (provisional).pdf

55-mum-2006-form-26.pdf

55-mum-2006-form-3.pdf

55-mum-2006-form-5.pdf

55-MUM-2006-REPLY TO EXAMNIATION REPORT(25-8-2009).pdf

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