Title of Invention

NOVEL INTERMEDIATE USEFUL FOR THE PREPARATION OF TOLTERODINE, A PROCESS FOR THE PREPARATION OF THE SAID INTERMEDIATE

Abstract

The invention disclosed in this application relates to novel compound N,N-diisopropyl-3-(2- Hydroxy-5-methylphenyl)-3-phenyl propionamide of the formula (1). The compound of the formula (1) is useful as an intermediate the preparation of tolterodine. The invention also relates to a process for the preparation of the said intermediate and an improved process for the preparation of tolterodine using the said intermediate. The process comprises of (i) Preparing the N,N-diisopropyl-3-(3-methoxy-5-methylphenyl)3-Phenyl-Propionamide of the formula (XI) by conventional methods. (ii) Demethylating the compound of the formula (XI) with Hydrobromic acid / acetic acid t, produce novel compound of the formula (1), (iii) reducing the novel compound of the formula 1 with sodium bis (2-methoxyethoxy) aluminohydride (VITRIDE) of the formula (2) yields tolterodine of the formula (VII) as hydrochloride salt.

Full Text

INTRODUCTION; The present invention relates to novel N,N-diisopropyl-3-(2-Hydroxy-5-methylphenyl)-3-phenyl propionamide. The novel N,N-diisopropyl-3-(2-Hydroxy-5-methylphenyl)-3-Phenyl propionamide has the formula (1) (1) The novel N,N-diisopropyl-3-(2-Hydroxy-5-methyl phenyl)-3-PhenyI propionamide is useful as an intermediate for the preparation of tolterodine of the formula (VII) as hydrochloride salt. Tolterodine hydrochloride on resolution with L(+)tartaric acid by conventional methods yields R- tolterodine-L-tartrate of the formula (VIII) \ - / R" tolterodine-L-tartrate of the formula (VIII) is useful in treating urinary incontinence BACKGROUND OF INVENTION Two methods for the preparation of R- tolterodine-L-tartrate of the formula (VIII) have been disclosed in EP-0325571 (1989). This process has been illustrated in the scheme shown in Fig 1 This method comprises the reaction of 6-methyl-4-phenyl-3,4-dihydro-2 H-1-benzopyran of the formula (1) with methyl iodide and potassium carbonate in refluxing acetone methanol gives 3-(2-methoxy-5-methylphenyl)-3-Phenylpropionic acid methyl ester of the formula (II), which on reduction with lithium aluminum hydride to the corresponding propanol of the formula (III). The reaction of the compound of the formula (III) with tosyl chloride and pyridine yields the tosylate of the formula (IV), which by condensation with diisopropylamine of the formula (V) in hot acetonitrile is converted into the tertiary amine of the formula (VI). Finally, this compound is treated with borontribromide in dichloromethane to afford the Tolterodine of the formula (VII) as a racemic mixture, which is resolved with L-(+)-tartaric acid This method suffers from the following drawbacks, 1. It involves the usage of boron tribromide solution for the preparation of compounds of formula (Vn). Boron tribronude is very corrosive, moisture sensitive, toxic and it's availability on commercial scale is very difficult 2. Second reagent for the preparation of the compound of the formula (VTI) is pyridine hydrochloride at a temperature in the range of 200-205°C. These high temperatures are not possible for scale-up batches. Attempted batches resulted in tarry materials which are difficult to separate from product with quantitative yields. 3. The process involves pyridine as a solvent for the preparation of the compound of the formula (IV) which is obnoxious and difficult to handle for commercial batches 4. The preparation of the compound of the formula (VI) involves special equipment i.e., pressure bottle at 80°C for 4-6 days 5. The use of lithium aluminum hydride in diethyl ether is an inflammable step. Second method is illustrated in the scheme shown in Fig 2 This method comprises the reaction of 3-(2-methoxy-5-methylphenyl)-3-phenyl propionic acid of the formula (IX) with thionyl chloride gives 3-(2-methoxy-5-methylphenyl)-3-phenyl propionyl chloride of the formula (X), which on reaction with diisopropylamine gives corresponding amide of formula (XI). The reduction of compound of formula (XI) with lithium aluminum hydride in diethyl ether solvent gives corresponding amine of formula(VI), Finally this compound is treated with borontribromide in dichloromethane to afford the tolterodine of the formula (VII) as a racemic mixture, which is resolved with L-(+)tartaric acid. This method suffers from the following draw backs : 1. By this process the compound of formula (VI) is obtained in 89% purity. 2. SO fumarate salt formation and its liberation is necessary to purify the compound of formula (VI) which adds further steps to the process thus making total process multi-step and low yielding 3. It also involves borontribromide (or) pyridinium chloride for the preparation of the compound of formula (VII) which cannot be used for commercial production. 4. It involves lithium aluminum hydride in diethyl ether for the preparation of the compound of the formula (VI) which is highly inflammable. Another method has been described in WO9829402A1 (1998). This is illustrated in the scheme shown in Fig -3 This process comprises the reduction of 3,4-dihydro-6-methyl-4-phenyl-2-H-benzopyan-2-one of the formula (1) with lithium tri-tert-butoxy alumino hydride (LITTBAL) gives 3,4-dihydro-6-methyl-4-phenyl-2-H-benzopyan-2-ol of the formula (II). For this reduction two other reducing agents that is diisobutylaluminohydride (DIBAL) and sodiumbismethoxyethoxyalumino hydride (VTRIDE) are also claimed. The compound of formula (II) on reductive amination with 5% Pd-C and diisopropylamine in pressure bottle gives racemic tolterodine of formula (VII) which is resolved with L-(H-)tartaric acid. The synthetic route outlined in the patent is afflicted by a serious draw back, namely he use of DIBAL / LITTBAL as the reduction reagent which works in stoichiometric amount with respect to lactone at low temperature, in addition it is sensitive to air and moisture. VITRIDE is also claimed as reducing agent but, experiments realized that diol (3) is obtained as byproduct along with pure lactol (XII) which is difficult to separate and became a potential impurity in that process. Yet another method has been described in organic process research and development 2002, 6, 379,383. This is illustrated in the scheme shown in Fig 4 P-cresol of formula (Xm) on reaction with phenyl acetylene of formula (XIV) gives l-[(2-Hydroxy-5-methyl)phenyl]-l-phenyl ethylene of the formula (XV), The compound of formula (XV) on hydroformylation with syngas in presence of rhodium catalyst at 100 atm. Pressure at 80-100oC for 24 -72 hours gives 3,6-dihydro-6-methyl4-phenyl-2H-benzopyran-2-ol of the formula (XVII). The compound of formula (XVII) on reductive amination with 5% Pd-C and diisopropylamine in pressure bottle gives racemic tolterodine of formula (VII) This process is described in 1-gram scale. This is not adaptable for multi-kilogram scale as it involves the following 1. Very expensive rhodium catalyst. 2. Specially designed high-pressure vessel. In J. Org. Chem 1998, 63 8067 - 8070 a process for an asymmetric synthesis via copper assisted asymmetric conjugate addition of aryl grignard reagents to 3-phenyl-l-prop-2-enoyl-oxazolidinones is described. This is illustrated by Fig-5 Fig-5 The oxazolidinone of formula (XVIII) on conjugate addition with l-benzyloxy-2.bromo-4-methyl benzene of formula (XIX) in copper bromide-dimethyl sulfide complex presence yields (5S)-phenyl-(3R)-(2-benzyloxy-5-methylphenyl)-3-phenylpropanoyl-2-oxazolidinone of formula (XX). The compound of formula (XX) is hydrolysed with lithium hydroxide to yield (3R)-(2-benzyloxy-5-methylphenyl)-3-phenyl-propanoic acid of formula (XXI). Compound of formula (XXI) on reaction with N,N-diisopropyl amine yields N,N-diisopropyl-(3R)-(2-benzyloxy-5-methyl phenyl)-3-phenyl propane amide of formula (XXII). The compound of formula (XXII) on hydrogenation yields tolterodine of formula (VII) This process is described in milligram scale. This cannot be adaptable for multi-kilogram scale because of the special reagents and conditions. It is very important to examine a process of preparing the compound of the formula (VII) from the point of industrial applicability whether the procedure fulfills the following requirements, 1. The starting materials for the process are easily available and as cheap as possible. 2. The use of harmful reagents are avoided during the course of the process. 3. The process should be safe from the point of environmental protection. 4. The formation of by-products and ballast materials, which cannot be used or processed further, should be minimized during the course of the process. 5. The reaction vessels generally used in pharmaceutical and chemical industry should be applicable for the carrying out the process. In other words there should not be any special or complicated or sophisticated apparatus required for carrying out the process. 6. It is also very important, that the process should result in the formation of pure final product, which does not need further expensive purification. All of the processes described above in the prior art do not fulfill one or other of the above conditions. Therefore we directed our R & D program to develop an improved process for the preparation of tolterodine of the formula VII taking into consideration the above mentioned requirements. The aim being to provide a new environmentally protective, safe, industrially applicable process, which was devoid of the insufficiencies of the known procedures and makes possible the synthesis of optically pure compound of the formula VII in high yields and was easily realizable industrially. Summary of invention; Accordingly we directed our research based on the under mentioned points • Avoiding the usage of borontribromide for demethylation • Avoiding the usage of lithium aluminum hydride • Avoiding the usage of flammable and obnoxious solvents • Avoiding special equipments • Reducing the number of purification steps • Improvement in the over all yields • Stabilization of final product • To demethylate N,N-diisopropyl 3-(2-methoxy-5-methylphenyl)-3- phenyl propionamide of the formula (XI) with hydrobromic acid/ acetic acid to produce novel compound N,N-diisopropyl-3-(2-hydroxy-5-methyl phenyl)-3- pehnyl propionamide of formula (1) which needs no further purification. • To reduce the novel compound of the formula (1) with vitride of the formula (2) to produce tolterodine of the formula (VII) as hydrochloride salt. Therefore the main objective of the present invention is to provide an improved process for the preparation of tolterodine of formula (VII) avoiding the drawbacks of the hitherto knoAvn processes. Another objective of the present invention is to provide an improved process for the preparation of tolterodine of formula (VII) avoiding the usage of borontribromide for demethylation. Yet another objective of the present invention is to provide an improved process for the preparation of tolterodine of formula (VII) avoiding the usage of lithium aluminum hydride. Still another objective of the present invention is to provide an improved process for the preparation of tolterodine of formula (VII) avoiding the usage of flammable and obnoxious solvents Another objective of the present invention is to provide an improved process for the preparation of tolterodine of formula (VII) avoiding special equipments. Yet another objective of the present invention is to provide an improved process for the preparation of tolterodine of formula (VII) reducing the number of purification steps. Still another objective of the present invention is to provide an improved process for the preparation of tolterodine of formula (VII) in which the over all yields is improved . Yet another objective of the present invention is to provide an improved process for the preparation of toherodine of formula (VII) in which stabilization is achieved . Another objective of the present invention is to provide novel intermediate of the formula 1 useful for the preparation of the compound of the formula VII. Yet another objective of the present invention is to provide a process for the preparation of novel intermediate of the formula I useful for the preparation of the compound of the formula VII. In our sustjuned R & D to achieve the above objectives we observed that the demethylation step could be carried in the presence of amide group present on side chain of compound of We also found further that HBr - acetic acid used in the demethylation step gave better quality and yield than the boron bromide method (30-35% higher overall yield) Accordingly the present invention provides an improved process for the preparation of novel compound of the formula (1) useful as an intermediate for the preparation of tolterodine of the formula (VII) Which comprises: i. Preparing N,N-diisopropyl -3- (2"methoxy-5-methyl phenyl)3-phenyl propionamide of the formula (XI) by conventional methods. ii. Demethylating the crude methoxy compound of the formula (XI) with hydrobromic acid / acetic acid in the temperature in the range of 50-90oC, to produce the novel compound of the formula (1) iii. Isolating the demethylated product of the formula (1) by quenching in a mixture of isopropyl ether and water (or) in a mixture of methylene chloride and water iv. Recrystallization of the compound of formula (1) with toluene and V. Reducing the novel compound of formula (1) with vitride to yield tolterodine of the formula (VII) as hydrochloride salt. The N,N-Diisopropyl -3- (2-methoxy-5-methyl phenyl)-3- phenyl propionamide of the formula (XI) used as the starting material in the step (i) may be prepared as per the process shown the reaction scheme in fig (2) as described in EP 0325571 (1989). For example N,N-Diisopropyl"3- (2-methoxy-5-methyl phenyl)-3- phenyl propionamide of the formula (XI) can be prepared as follows. 3- (2-methoxy-5-methyl phenyl)-3- phenyl propionic acid of the formula (IX) on reaction with thionyl chloride yields 3- (2-methoxy-5-methyl phenyl)-3- phenyl propionyl chloride of the formula (X). The Compound of the formula (X) on treatment with N,N-Diisopropyl amine yields compound of formula (XI). The concentration of the Hydrobromic acetic acid used in step (ii) may be in the range of 28-33% preferably in the range of 31-33%. The volume of hydrobromic acid acetic acid with respect to the weight of compound of the formula (XI) may be in the range of 3-8 volumes preferably in the range of 4-5 volumes. The temperature employed may be in the range of 50-90°C preferably in the range of 80-90°C the reaction time may be in the range of 6-12 hours preferably in the range of 8-10 hours. The amount of vitride used in step (iii) may be in the range of 2-3 moles , preferably 3 moles. The reaction temperature may be in the range of 50-80^C preferably in the range of 60-70^C. The reaction time may be in the range of 1 to 5 hours, preferably in the range of 2-3 hours. After work up hydrochloride salt of tolterodine of the formula (VII) may be done in ethylacetate, ethanol (or) acetone, preferably acetone. The reaction scheme for the preparation of tolterodine the formula (VII) according to the present invention is shown in the Fig -6 The details of the inventions are given in the Examples given below which are provided for illustration only and therefore these examples should not be constructed to limit the scope of the invention. Example-1; The preparation of N,N-diisopropyl-3-(2-Hydroxy-5-methylphenyl)-3-Phenyl propionamide of the formula :(1) Raw materials 1. N,N-diisopropyl-3-(2-methoxy-5-methylphenyl)-3-Phenyl propionamide of the formula (XI) 3.0 Kg 2. HBr-acetic acid (33%) - 16.0 Lts 3. Methylene chloride - 25.0 Lts 4. Isopropyl ether (IPE) - 15.0 Lts 5. Toluene - 7.0 Lts 6. Activated carbon - 0.15 Kg Procedure: Into the reactor 3.0 kgs of N,N-diisopropyl-3-(2-methoxy-5-methylphenyl)-3-Phenyl propionamide of the formula (XI) is charged. 16.0 L of hydrobromic acid in acetic acid is charged. The reaction mixture is heated to 80-90°C and maintained for 9-10 hours at 80-90°C. The completion of the reaction is checked by thin layer chromatography. The reaction mass is brought to room temperature. It is poured into a mixture of 30.0 L of DM water and 6.0 L Isopropyl ether at RT slowly during 15-30 minutes. It is stirred well till product is separated out in fine form centrifuged and slurry washed thoroughly with DM water and Isopropyl ether. Centrifuged the wet compound and is dissolved in 25.0 L Methylene chloride. Organic layer is separated and is dried over sodium sulfate. Carbon treatment is given to Methylene chloride layer at room temperature. Methylene chloride is distilled off completely under vacuum. The residue is recrystallized from toluene. Dried in oven at 50-60°C under vacuum [1.8 Kg, 62.6%; MR-170-173°C] Analysis: C22H29NO2 Molecular weight: 339.0 IR Spectrum - KBr disc Absence of-OCHa -OH at 3135.7 UV spectrum -Methanol X max at - 283nm X min at - 249nm 1HNMR (CDCI3) 9,2 (s, IH, Ar1-OH)D2O exchangeable : 7.3-7.2 (m,5H,Ar); 6.62(d,lH,Ar1) ;6.84 (d,2H,Ar^) 5.0(t,lH, ArAr1CH); 4.0-4.1 (m, 1H,CH(CH3)2); 3.3-3.6 (m, 1H,CH(CH3)2); 3.0-3.l(d,2H,-CH2-C0); 2.1 (s, 3H,Ar1.CH3); 1.1-1.6 (4d, 12H, 2[CH(CH3)2] 13CNMR (CDCI3)- 5171.6[CON(CHCH3)2], 118-152.1(Ar,Ar^); 48.7 (Ar,Ar^C), 46.2(CH2CO),38.7,40.9[CH (CH3)2]; 20.3-20.6 [CH (3)2]; The preparation of N,N-diisopropyl-3-(2-Hydroxy-5-methylphenyl)-3-Phenyl propylamine ofthe formula (VII) Raw materials 1. N,N-diisopropyI-3-(2-Hydroxy-5-methylphenyl)-3-Phenyl propionamide (I) - 2.3 Kg 2. Vitride(60% solution in toluene) - 6.4 Lts 3. Toluene - 15.0+12.0 Lts 4. 8% sodium hydroxide solution - 90.0 Lts 5. Acetone - 10.0 Lts 6. Cone. Hydrochloric acid - 0.7 Lts Procedure : Into the reactor 15.0 Lts of toluene is charged under nitrogen atmosphere. 6.4 kgs of vitride is also charged into the reactor. 2.3 Kgs of N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-Phenyl propionamide prepared as described above is suspended in 12.0 Lts toluene is also charged slowly during 2-3 hours at 25-40°C. Heated to 60-70'C. Maintained 60-70°C for 3-4 hours. Reaction completion is checked by thin layer chromatography. Reaction mass is quenched into 90.0 Lts of 8% sodium hydroxide solution during 30 minutes at RT under stirring. Toluene layer is separated out and washed thoroughly with DM water, dried over sodium sulfate. Toluene is distilled off completely under vacuum. Residue is brought to room temperature. 10.0 Lts of acetone is charged to the residue. About 0.7 Lts of cone. Hydrochloric acid is added slowly during a period of 30-45 minutes. Reaction mass is cooled to 0-5°C and maintained 8 hours at that temperature. Centrifuged and washed with 2.0 Its chilled acetone. Dried under vacuum at 50-60X [1.84 Kg, 74.7%; MR-218-220°C] Example 2 The preparation of N,N-diisopropyl-3-(2-Hydroxy-5-methylphenyl)-3-Phenyl propionamide of the formula :(1) Raw materials 1. N,N-diisopropyl-3-(2-methoxy-5-methylphenyl)-3-Phenyl propionamideof the formula (XI) 3.0 Kg 2. HBr - acetic acid (33%) - 16.0 Lts 3. Methylene chloride - 35.0 Lts 4. Toluene - 15.0 Lts 5. Activated carbon - 0.15 Kg Procedure: Into the reactor 3.0 kgs of N,N-diisopropyl-3-(2-methoxy-5-methylphenyl)-3-Phenyl propionamide of the formula (XI) is charged. 16.0 L of hydrobromic acid in acetic acid is charged. The reaction mixture is heated to 80-90°C and maintained for 9-10 hours at 80-90°C. The completion of the reaction is checked by thin layer chromatography. The reaction mass is brought to room temperature. It is poured into 30.0 L of DM water and 10-L methylene chloride under stirring. Organic layer is separated and washed with 1% sodium bicarbonate solution and DM water. Methylene chloride is distilled off completely under vacuum. The residue is recrystallised twice with toluene to yield compound of formula (1). Dried in oven at 50-60°C under vacuum [1.7 Kg, 59.1%; MR-168-170°C] Analysis: C22H29NO2 Molecular weight: 339.0 IR, 1HNMR (CDCl3) and 13CNMR were consistent with the proposed structure The preparation of N,N-diisopropyl-3-(2-Hydroxy-5-methylphenyl)-3-Phenyl propylamine ofthe formula (VII) Raw materials 1. N,N-diisopropyI-3-(2-Hydroxy-5-methylphenyl)-3-Phenyl propionamide (I) - 2.3 Kg 2. Vitride(60% solution in toluene) - 6.4 Lts 3. Toluene - 15.0+12.0 Lts 4. 8% sodium hydroxide solution - 90.0 Lts 5. Ethyl acetate - 12.0 Lts 6. Cone. Hydrochloric acid - 0.7 Lts Procedure: Into the reactor 15.0 Lts of toluene is charged under nitrogen atmosphere. 6.4 kgs of vitride is also charged into the reactor. 2.3 Kgs of N,N-diisopropyI-3-(2-hydroxy-5-methylphenyl)-3-Phenyl propionamide prepared as described above is suspended in 12.0 Lts toluene is also charged slowly during 2-3 hours at 25-40°. Heated to 60-70° Maintained 60-70° for 3-4 hours. Reaction completion is checked by thin layer chromatography. Reaction mass is quenched into 90.0 Lts of 8% sodium hydroxide solution during 30 minutes at RT under stirring. Toluene layer is separated out and washed thoroughly with DM water, dried over sodium sulfate. Toluene is distilled off completely under vacuum. Residue is brought to room temperature. 10.0 Lts of ethyl acetate is charged to the residue. Heated to 45 to 50 °C. About 0.7 Lts of cone. Hydrochloric acid is added slowly during a period of 30-45 minutes. Reaction mass is cooled to 0-5°C and maintained 2-3 hours at that temperature. Centrifuged and washed with 2.0 Us chilled ethyl acetate. Dried under vacuum at SO-GC^C [1.9 Kg, 77.1%; MR-218-220°C] Advantages of the present process 1. The process resuhs in getting stabilized final product. 2. Improvement of overall yields (about 30%), 3. Avoiding harmful reagents thus protecting environment, 4. Simple and industrially applicable process . 5. Avoiding the usage of lithium aluminum hydride. 6. Avoiding special equipments. 7. Reducing the number of purification steps thereby making the process economical. WE CLAIM 1.Novel N,N-diisopropyl-3-(2-Hydroxy-5-methylphenyl)-3-phenyl propionamide of the formula 1 useful for the preparation of tolterodine of the formula VII 2. A improved process for the preparation of novel compound of the formula (1) useful as an intermediate for the preparation of tolterodine of the formula (VII) Which comprises: (i) Preparing N,N-diisopropyl -3- (2-methoxy-5-methyl pheny 1)3-phenyl propianomide of the formula (XI) by conventional methods. (ii) Demethylating the crude methoxy compound of the formula (XI) with hydrobromic acid / acetic acid in the temperature in the range of 50-90°C, to produce the novel compound of the formula (1). (iii) isolating the demethylated product of the formula (1) by quenching in a mixture of isopropyl ether and water 3. A process as claimed in claim 2 wherein the N,N-Diisopropyl -3- (2-methoxy-5-methyl phenyl)-3- phenyl propionamide of the formula (XI) used as the starting material in the step (i) is prepared as per the process shown the reaction scheme in fig (2) as described in EP 0325571 (1989). 4. An improved process as claimed in claims 2 & 3 wherein the concentration of the Hydrobromic acetic acid used in step (ii) is in the range of 28-33%, preferably in the range of 31-33%. 5. An improved process as claimed in claims 2 to 4 wherein the volume of hydrobromic acid acetic acid used with respect to the weight of compound of the formula (XI) is in the range of 3-8 volumes, preferably in the range of 4-5 volumes. 6. An improved process as claimed in claims 2 to 5 wherein the temperature employed is in the range of 50-90^C, preferably in the range of 80-90°C 7. An improved process as claimed in claim 2 to 6 wherein the reaction time is in the range of 6-12 hours preferably in the range of 8-10 hours 8. An improved process for the preparation of the tolterodine of the formula (VII) which comprises: (i) Preparing N,N-diisopropyl -3- (2-methoxy-5-methyl phenyl)3-phenyl propianomide of the formula (XI) by conventional methods. (ii) Demethylating the crude methoxy compound of the formula (XI) with hydrobromic acid / acetic acid in the temperature in the range of 50-90°C, to produce the novel compound of the formula (1) (iii) isolating the demethylated product of the formula (1) by quenching in a mixture of isopropyl ether and water and (iv) reducing the novel compound of formula (1) with vitride to yield tolterodine of the formula (VII) as hydrochloride salt. 9. An improved process as claimed in claim 8 wherein the N,N-Diisopropyl -3- (2- methoxy-5-methyl phenyl)-3- phenyl propionamide of the formula (XI) used as the starting material in the step (i) is prepared as per the process shown the reaction scheme in fig (2) as described in EP 0325571 (1989) . 10. An improved process as claimed in claims 8 & 9 wherein the concentration of the Hydrobromic acetic acid used in step (ii) is in the range of 28-33%, preferably in the range of 31-33%. 11. An improved process as claimed in claims 8 to 10 wherein the volume of hydrobromic acid acetic acid used with respect to the weight of compound of the formula (XI) is in the range of 3-8 volumes, preferably in the range of 4-5 volumes. 12. An improved process as claimed in claims 8 to 11 wherein the temperature employed is in the range of 50-90°C, preferably in the range of 80-90°C . 13. An improved process as claimed in claim 8 to 12 wherein the reaction time is in the range of 6-12 hours preferably in the range of 8-10 hours. 14. An improved process as claimed in claims 8 to 13 wherein The amount of vitride used in step (iii) is in the range of 2-3 moles, preferably 3 moles. 15. An improved process as claimed in claims 8 to 14 wherein the reaction temperature is in the range of 50-80°C preferably in the range of 60-70°C, 16. An improved process as claimed in claims 8 to 15 wherein the reaction time is in the range of 1 to 5 hours, preferably in the range of 2-3 hours. 17. An improved process as claimed in claim 8 to 16 wherein the hydrochloride salt of tolterodine of the formula (VII) can be done using ethylacetate, ethanol (or) acetone, preferably acetone. 18 A process for the preparation of novel compound of the formula 1 substantially as herein described with reference to the examples. 19. An improved process for the preparation of compound of the formula VII substantially as herein described with reference to the examples.

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