Title of Invention	A process for the preparation of a novel 3-oxo-5-(tert.butyldimethylsilyloxy)-(1S, 5S)-cyclohexylacetate useful as an intermediate for Beta-hydroxy-Gama-lactone
Abstract	The present invention provides a process for the preparation of a novel 3-oxo-5-(tert.butyldimethylsilyloxy)-(1S, 55)-cyclohexylacetate having formula 6 useful as an intermediate for 6-hydroxymethyl-4-(tert-butyldimethylsilyloxy)-(4R,6S)-tetrahydro-2H-2-pyranone. More particularly the present invention provides a process for the preparation of a novel 3-oxo-5-(tert.butyldimethylsilyloxy)-(1S, 55)-cyclohexylacetate having formula (6) from 3-hydroxy-5-(tert.butyldimethylsilyloxy)-(lS,3R,5R)-cyclohexylacetate having formula 5

Title of Invention

A process for the preparation of a novel 3-oxo-5-(tert.butyldimethylsilyloxy)-(1S, 5S)-cyclohexylacetate useful as an intermediate for Beta-hydroxy-Gama-lactone

Abstract

The present invention provides a process for the preparation of a novel 3-oxo-5-(tert.butyldimethylsilyloxy)-(1S, 55)-cyclohexylacetate having formula 6 useful as an intermediate for 6-hydroxymethyl-4-(tert-butyldimethylsilyloxy)-(4R,6S)-tetrahydro-2H-2-pyranone. More particularly the present invention provides a process for the preparation of a novel 3-oxo-5-(tert.butyldimethylsilyloxy)-(1S, 55)-cyclohexylacetate having formula (6) from 3-hydroxy-5-(tert.butyldimethylsilyloxy)-(lS,3R,5R)-cyclohexylacetate having formula 5

Full Text	The present relates to a process for the preparation of a novel 3-oxo-5-(tert.butyldimethylsilyloxy)-(1S,5S)-cyclohexylacetate having formula 6 (Formula Removed) useful as an intermediate for 6-hydroxymethyl-4-(tert-butyldimethylsilyloxy)-(4R,6S)-tetrahydro-2H-2-pyranone for ß-hydroxy -lactone. More particularly the present invention relates to a process for the preparation of a novel 3-oxo-5-(tert.butyldimethylsilyloxy)-(1S,5S)--cyclohexylacetate having formula (6) from 3-hydroxy-5-(tert.butyldimethylsilyloxy)-(1S,3R,5R)-cyclohexylacetate having formula 5 (Formula Removed) The compound 3-hydroxy-5-(tert.butyldimethylsilyloxy)-(1S,3R,5R)-cyclo-hexylacetate having formula 5 is prepared by a procedure as described and claimed in our co-pending application No.81/Del/2001. The compound ß-hydroxy δ-lactone is an important intermediate in the synthesis of biologically active drugs e.g. compactin, atorvastatin, fluvastatin, cholesterol lowering drugs. Hitherto known processes for the synthesis of ß-hydroxy-δ-lactone (1) involves a) Enzymatic kinetic resolution of racemic ß-hydroxy-δ-lactone by transesterification with vinyl acetate in THF using Chromobacteriun viscosum lipase as catalyst at 40°C. [Crosby, J. B.; Andrew, J. H.; John, A. L. WO 9306235 Al CA 119:936292 (1993)] b) Chemoenzymatic route involving kinetic resolution through lactone formation in ether catalyzed by PPL [Bonini, C; Pucci, P.; Viggiani, L. J. Org. Chem. 1991,56,4050] c) Chemoenzymatic route involving enzymatic desymmetrization of intermediate diacetate, followed by chemical conversions. [Bonni, C; Racioppi, R.; Righi, G.; Viggiani, L. J. Org. Chem. 1991, 58, 802] The prior art processes have following drawbacks: 1. The processes use chemicals such as butyl lithium, lithium aluminum hydride, methoxydiethylborane that are costly and difficult to handle and therefore make the process difficult. 2. All known process are however involves large number of synthetic steps resulting in low over all yields. The main object of the present invention is to provide a process for the preparation of a novel 3-oxo-5-(tert.butyldimethylsilyloxy)-(l,S,5S)-cyclohexylacetate useful as an intermediate for 6-hydroxymethyl-4-(tert-butyldimethylsilyloxy)-(4S,6R)-tetrahydro-2H-2-pyranone (ß-hydroxy-δ-lactone) (1). Another object is to provide a process for the preparation of 6-hydroxymethyl-4-(tert-butyldimethylsilyloxy)-(4R,6S)-tetrahydro-2H-2-pyranone (ß-hydroxy δ-lactone) which obviates the drawbacks of the prior art processes and use cheaper and easily accessible chemicals. Accordingly, the present invention provides a process for the preparation of a novel 3-oxo-5-(tert.butyldimethylsilyloxy)-(1S,5S)-cyclohexylacetate having formula 6 (Formula Removed) useful as an intermediate for ß-hydroxy lactone which comprises extracting 3-hydroxy-5-(tert.butyldimethylsilyloxy)-(1S,3R,5R)-cyclohexylacetate having formula 5 in an organic solvent with chlorochromate of tertiary amines at a temperature ranging from 10-30°C, quenching the above reaction by adding diethyl ether, filtering the mixture through ceilite and washing with brine, removing the solvent by evaporation, followed by fast column filtration to obtain 3-oxo-5-(tert.butyldimethylsilyloxy)-(1S,5S)-cyclohexylacetate. In an embodiment of the present invention the organic solvent used for the reaction is selected from the group consisting of ethyl acetate, chloroform and dichloromethane. The process of the present invention is described herein below with references to the following examples, which are illustrative only and should not be construed to unit the scope of the present invention in any manner. Example 1 Preparation of cis, cis-3-hydroxy-5-methylcarbonyloxy-cyclohexylacetate 3: Finely powdered cis, cis-3,5-di(methylcarbonyloxy)cyclohexylacetate 2 (6.5 parts, 25.19 mmol parts) was suspended in 0.1 M sodium phosphate buffer (pH 7) (135 parts) and stirred vigorously. To the stirred suspension Porcine Liver Esterase (0.110 parts) was added and reaction mixture was stirred vigorously at 30°C for 20 hr. pH of the reaction mixture was monitored at every 2 hrs and was maintained at pH 7 using IN NaOH solution. After completion of reaction (20 hr), it was extracted with ethyl acetate (2 x 150 parts). Organic layers were combined and washed with brine, dried on anhydrous sodium sulfate and concentrated under vacuum to yield cis,cis-3- hydroxy-5-methylcarbonyloxycyclohexylacetate 3 yield (4.8 g parts, 88%). 1H NMR(CDC13): δ 1.20-1.58 (qn, 3H), 2.08 (s, 6H), 2.28 (m, 3H), 3.78 (m, 1H), 4.78 (m, 2H) 13C NMR (CDC13): δ 21.15, 36.33, 39.93, 64.83, 67.65, 170.42 IR(KBr): 754.60, 884.15, 1029.29, 1140.34, 1250.00, 1367.64, 1738.92,2871.17, 2953.14,3445.47 Mass: Base m/e = 96 other m/e: 156, 138, 114, 73, 67, 67, 60, 55 Elemental analysis: calculated for Cl0H16O5: C 55.56%, H 7.40% Found : C 55.30%, H 8.00% Example 2 Preparation of cis,cis-3-(methylcarbonyloxy)-5-(tert.butyldimethylsilyloxy)cyclo- hexylacetate 4 Cis, cis-3-hydroxy-5-methylcarbonyloxy-cyclohexylacetate (3, 2 parts, 9.26 mmol) and DMAP (0.113 parts, 0.926 mmol) were placed in 100 ml two-necked round bottom flask equipped with dropping funnel and two-way stopcock. It was evacuated and flushed with argon. To it, dry dichloromethane (10 parts) and dry HMPA (2 part) was added and stirred to dissolve. The solution was cooled to -10°C with stirring. To it, solution of tert-butyldimethylsilyl chloride in 10 part dry dichloromethane was added dropwise while maintaining temperature below 0°C. Reaction mixture was stirred for 15 min and to it dry triethylamine (2.02 parts, 20 mmol) was added dropwise. Reaction mixture was stirred at room temperature for 12 hr. It was then transferred to a separating funnel and washed successively with cold, dil. HC1 water, aq. NaHCO3 and then brine. Organic layer was dried on anhydrous sodium sulfate and solvent was removed under vacuum. Residue was purified by flash column chromatography, (eluent 2-4% ethyl acetate in petroleum ether) to yield Cis,cis-3- (methylcarbonyloxy)-5-(tert.butyldimethylsilyloxy)cyclohexylacetate (4, yield 2.85 parts, 90%). 1H NMR (CDC13): δ 0.06(s, 9H), 0.87 (s, 6H), 1.20-1.45 (m, 3H), 2.03 (s, 6H), 2.2 (m, 3H), 3.38 (m, 1H), 4.73 (m, 2H). I3C NMR (CDCl3): δ -5.07, 17.61,25.40, 36.17, 40.40, 65.43, 67.01, 169.64 IR(CHC13): 758.90,838.05, 1034.91, 1106.32, 1246.82, 1368.91, 1734.01,2858.81, 2955.07 Mass: Base m/e= 117 other m/e: 273,213, 171, 159, 129, 117,97,79,75,57 Elemental analysis: calculated for C26H30O5Si: C 58.185%, H 9.10% Found : C 58.19%, H 9.50% Example 3 Preparation of 3-hydroxy-5-(tert.butyldimethylsilyloxy)-(lS,3R,5R)-cyclohexyl acetate (5) Cis, cis-3-(methylcarbonyloxy)-5-(tert.butyldimethylsilyloxy)cyclohexylacetate (4, 5 patrs, 147 mmol) was dissolved in tert-butanol (20 parts). To the solution, 0.1 M sodium phosphate buffer (230 parts, pH 8) was added and mixture was stirred vigorously. To the stirred emulsion, Porcine liver esterase (0.150 parts) was added and the mixture was stirred vigorously at 30°C for 54 hrs. During reaction pH was maintained at 8 using IN sodium hydroxide solution. Reaction mixture was extracted with ethyl acetate (3 x 200 parts). Organic layers were combined and washed with brine. It was then dried on anhydrous sodium sulfate and solvent was removed under vacuum. Oily residue contained 3-hydroxy-5-(tert.butyldimethylsilyloxy)- (lS,3R,5R)-cyclohexylacetate 5 along with unreacted 4. Both were separated by flash column chromatography. Cis,cis-3-(methylcarbonyloxy)-5-(tert.butyldimethylsilyloxy)cyclohexylacetate: (4, 1.07 parts; 3-hydroxy-5-(tert.butyldimethylsilyloxy)-(lS,3R,5R)-cyclohexylacetate: (5, 2.8 parts, 70% based on recovered starting material). 1H NMR (CDC13): δ 0.06 (s, 9H), 0.87 (s, 6H), 1.35-1.60, (m, 3H), 2.06 (s, 3H), 2.15 (m, 3H), 3.7 (m, 2H), 4.75 (m, 1H) 13C NMR (CDCl3): δ -4.60, 18.15,21.38, 25.90, 39.98,40.31,43.93, 65.45, 66.40, 68.17, 170.68 IR(CHC13): 758.43, 838.93, 1049.42, 1109.15, 1218.09, 1254.01, 1370.09, 1725.03, 2859.8,2887.95, 2952.33, 3017.48 Mass: Base m/e = 75 other m/e: 231, 171, 129, 117, 105, 97, 79, 75, 67, 59 Elemental analysis: calculated for C14H28O4Si: C 58.33%, H 9.72% Found : C 58.15%, H 10.20% Specific rotation [α]D = - 4.8 (c 1, CHC13) e.e. >95% Example 4: Preparation of 3-oxo-5-(tert.butyIdimethylsilyloxy)-(1S', 5S)-cyclohexylacetate (6) Cis,cis-3-(methylcarbonyloxy)-5-(tert.butyldimethylsilyloxy)-(1S,3R,5R)-cyclohexyl- acetate (5, 1.40 parts, 2.78 mmol) was dissolved in dichloromethane 5 parts to the solution sodium acetate (0.1 part) and pyridinium chlorochromate (1.57 parts, 7.3 mmol) were added. The mixture was stirred for 5 hr at RT. Residue was extracted with ether (3x10 parts). Organic extracts were combined, filtered through ceilite. Filtrate was washed with brine:water (1:1), finally with brine. Organic layer was dried on anhydrous sodium sulphate and concentrated under vacuum. Residue was filtered through silica gel column to afford 3-oxo-5-(/er/.butyldimethylsilyloxy)-(15, 55)- cyclohexylacetate 6 (1.30 parts, 93.5%). 1H NMR (CDC13): δ 0.10 (d, 9H), 0.88 (d, 6H), 2.06 (s, 3H), 2.45 (m, 4H), 2.70 (m,2H), 4.00 (m, 1H), 5.00 (m, 1H) 13C NMR (CDCl3): δ -4.95, 17.82, 20.97, 25.57, 39.34, 45.93, 50.30, 65.98, 67.23, 169.87, 205.27 IR(CHC13): 442.57, 756.83, 1218.50, 1244.99, 1723.00, 2857.44, 2932.80, 2953.64, 3019.98 Mass: Base m/e = 163 other m/e: 185, 169, 145, 127, 117, 111, 101, 95, 75, 59 Elemental analysis: calculated for C14H26O4Si: C 58.74%, 9.09% Found : C 58.60%, H 9.8% Specific rotation [α]D = -11.54 (c 1, CHC13) We claim : 1. A process for the preparation of a novel 3-oxo-5-(tert.butyldimethylsilyloxy)- (1S,5S)-cyclohexylacetate having formula 6 (Formula Removed) useful as an intermediate for ß-hydroxy -lactone which comprises extracting 3-hydroxy-5-(tert.butyldimethylsilyloxy)-(1S,3R,5R)-cyclohexylacetate having formula 5 in an organic solvent with chlorochromate of tertiary amines at a temperature ranging from 10-30°C, quenching the above reaction by adding diethyl ether, filtering the mixture through ceilite and washing with brine, removing the solvent by evaporation, followed by fast column filtration to obtain 3-oxo-5-(tert.butyldimethylsilyloxy)-(1S,5S)-cyclohexylacetate. 2. A process as claimed in claim 1 wherein the organic solvent used for the reaction is selected from the group consisting of ethyl acetate, chloroform, dichloromethane. 3. A process for the preparation of a novel 3-oxo-5-(tert.butyldimethylsilyloxy)-(1S,5S)-cyclohexylacetate useful as an intermediate for ß-hydroxy δ-lactone useful as an intermediate for ß-hydroxy -lactone substantially as herein described with reference to the examples.

Full Text

The present relates to a process for the preparation of a novel 3-oxo-5-(tert.butyldimethylsilyloxy)-(1S,5S)-cyclohexylacetate having formula 6
(Formula Removed)
useful as an intermediate for 6-hydroxymethyl-4-(tert-butyldimethylsilyloxy)-(4R,6S)-tetrahydro-2H-2-pyranone for ß-hydroxy -lactone.
More particularly the present invention relates to a process for the preparation of a novel 3-oxo-5-(tert.butyldimethylsilyloxy)-(1S,5S)--cyclohexylacetate having formula (6) from 3-hydroxy-5-(tert.butyldimethylsilyloxy)-(1S,3R,5R)-cyclohexylacetate having formula 5
(Formula Removed)
The compound 3-hydroxy-5-(tert.butyldimethylsilyloxy)-(1S,3R,5R)-cyclo-hexylacetate having formula 5 is prepared by a procedure as described and claimed in our co-pending application No.81/Del/2001.
The compound ß-hydroxy δ-lactone is an important intermediate in the synthesis of biologically active drugs e.g. compactin, atorvastatin, fluvastatin, cholesterol lowering drugs.
Hitherto known processes for the synthesis of ß-hydroxy-δ-lactone (1) involves
a) Enzymatic kinetic resolution of racemic ß-hydroxy-δ-lactone by transesterification with vinyl acetate in THF using Chromobacteriun viscosum lipase as catalyst at 40°C. [Crosby, J. B.; Andrew, J. H.; John, A. L. WO 9306235 Al CA 119:936292 (1993)]
b) Chemoenzymatic route involving kinetic resolution through lactone formation in ether catalyzed by PPL [Bonini, C; Pucci, P.; Viggiani, L. J. Org. Chem. 1991,56,4050]
c) Chemoenzymatic route involving enzymatic desymmetrization of intermediate diacetate, followed by chemical conversions. [Bonni, C; Racioppi, R.; Righi, G.; Viggiani, L. J. Org. Chem. 1991, 58, 802]
The prior art processes have following drawbacks:
1. The processes use chemicals such as butyl lithium, lithium aluminum hydride, methoxydiethylborane that are costly and difficult to handle and therefore make the process difficult.
2. All known process are however involves large number of synthetic steps resulting in low over all yields.
The main object of the present invention is to provide a process for the preparation of a novel 3-oxo-5-(tert.butyldimethylsilyloxy)-(l,S,5S)-cyclohexylacetate useful as an intermediate for 6-hydroxymethyl-4-(tert-butyldimethylsilyloxy)-(4S,6R)-tetrahydro-2H-2-pyranone (ß-hydroxy-δ-lactone) (1).
Another object is to provide a process for the preparation of 6-hydroxymethyl-4-(tert-butyldimethylsilyloxy)-(4R,6S)-tetrahydro-2H-2-pyranone (ß-hydroxy δ-lactone) which obviates the drawbacks of the prior art processes and use cheaper and easily accessible chemicals.
Accordingly, the present invention provides a process for the preparation of a novel 3-oxo-5-(tert.butyldimethylsilyloxy)-(1S,5S)-cyclohexylacetate having formula 6
(Formula Removed)
useful as an intermediate for ß-hydroxy lactone which comprises extracting
3-hydroxy-5-(tert.butyldimethylsilyloxy)-(1S,3R,5R)-cyclohexylacetate having
formula 5 in an organic solvent with chlorochromate of tertiary amines at a temperature ranging from 10-30°C, quenching the above reaction by adding diethyl ether, filtering the mixture through ceilite and washing with brine, removing the solvent by evaporation, followed by fast column filtration to obtain 3-oxo-5-(tert.butyldimethylsilyloxy)-(1S,5S)-cyclohexylacetate.
In an embodiment of the present invention the organic solvent used for the reaction is selected from the group consisting of ethyl acetate, chloroform and dichloromethane.
The process of the present invention is described herein below with references to the following examples, which are illustrative only and should not be construed to unit the scope of the present invention in any manner.
Example 1
Preparation of cis, cis-3-hydroxy-5-methylcarbonyloxy-cyclohexylacetate 3:
Finely powdered cis, cis-3,5-di(methylcarbonyloxy)cyclohexylacetate 2 (6.5 parts,
25.19 mmol parts) was suspended in 0.1 M sodium phosphate buffer (pH 7) (135
parts) and stirred vigorously. To the stirred suspension Porcine Liver Esterase (0.110
parts) was added and reaction mixture was stirred vigorously at 30°C for 20 hr. pH of
the reaction mixture was monitored at every 2 hrs and was maintained at pH 7 using
IN NaOH solution. After completion of reaction (20 hr), it was extracted with ethyl
acetate (2 x 150 parts). Organic layers were combined and washed with brine, dried
on anhydrous sodium sulfate and concentrated under vacuum to yield cis,cis-3-
hydroxy-5-methylcarbonyloxycyclohexylacetate 3 yield (4.8 g parts, 88%).
1H NMR(CDC13): δ 1.20-1.58 (qn, 3H), 2.08 (s, 6H), 2.28 (m, 3H), 3.78 (m, 1H), 4.78 (m, 2H)
13C NMR (CDC13): δ 21.15, 36.33, 39.93, 64.83, 67.65, 170.42
IR(KBr): 754.60, 884.15, 1029.29, 1140.34, 1250.00, 1367.64, 1738.92,2871.17, 2953.14,3445.47
Mass: Base m/e = 96 other m/e: 156, 138, 114, 73, 67, 67, 60, 55
Elemental analysis: calculated for Cl0H16O5: C 55.56%, H 7.40%
Found : C 55.30%, H 8.00%
Example 2
Preparation of cis,cis-3-(methylcarbonyloxy)-5-(tert.butyldimethylsilyloxy)cyclo-
hexylacetate 4
Cis, cis-3-hydroxy-5-methylcarbonyloxy-cyclohexylacetate (3, 2 parts, 9.26 mmol)
and DMAP (0.113 parts, 0.926 mmol) were placed in 100 ml two-necked round
bottom flask equipped with dropping funnel and two-way stopcock. It was evacuated
and flushed with argon. To it, dry dichloromethane (10 parts) and dry HMPA (2 part)
was added and stirred to dissolve. The solution was cooled to -10°C with stirring. To
it, solution of tert-butyldimethylsilyl chloride in 10 part dry dichloromethane was
added dropwise while maintaining temperature below 0°C. Reaction mixture was
stirred for 15 min and to it dry triethylamine (2.02 parts, 20 mmol) was added
dropwise. Reaction mixture was stirred at room temperature for 12 hr. It was then
transferred to a separating funnel and washed successively with cold, dil. HC1 water,
aq. NaHCO3 and then brine. Organic layer was dried on anhydrous sodium sulfate
and solvent was removed under vacuum. Residue was purified by flash column
chromatography, (eluent 2-4% ethyl acetate in petroleum ether) to yield Cis,cis-3-
(methylcarbonyloxy)-5-(tert.butyldimethylsilyloxy)cyclohexylacetate (4, yield 2.85
parts, 90%).
1H NMR (CDC13): δ 0.06(s, 9H), 0.87 (s, 6H), 1.20-1.45 (m, 3H), 2.03 (s, 6H), 2.2 (m, 3H), 3.38 (m, 1H), 4.73 (m, 2H).
I3C NMR (CDCl3): δ -5.07, 17.61,25.40, 36.17, 40.40, 65.43, 67.01, 169.64
IR(CHC13): 758.90,838.05, 1034.91, 1106.32, 1246.82, 1368.91, 1734.01,2858.81, 2955.07
Mass: Base m/e= 117 other m/e: 273,213, 171, 159, 129, 117,97,79,75,57
Elemental analysis: calculated for C26H30O5Si: C 58.185%, H 9.10%
Found : C 58.19%, H 9.50%
Example 3
Preparation of 3-hydroxy-5-(tert.butyldimethylsilyloxy)-(lS,3R,5R)-cyclohexyl
acetate (5)
Cis, cis-3-(methylcarbonyloxy)-5-(tert.butyldimethylsilyloxy)cyclohexylacetate (4, 5
patrs, 147 mmol) was dissolved in tert-butanol (20 parts). To the solution, 0.1 M
sodium phosphate buffer (230 parts, pH 8) was added and mixture was stirred
vigorously. To the stirred emulsion, Porcine liver esterase (0.150 parts) was added
and the mixture was stirred vigorously at 30°C for 54 hrs. During reaction pH was
maintained at 8 using IN sodium hydroxide solution. Reaction mixture was extracted
with ethyl acetate (3 x 200 parts). Organic layers were combined and washed with
brine. It was then dried on anhydrous sodium sulfate and solvent was removed under
vacuum. Oily residue contained 3-hydroxy-5-(tert.butyldimethylsilyloxy)-
(lS,3R,5R)-cyclohexylacetate 5 along with unreacted 4. Both were separated by
flash column chromatography.
Cis,cis-3-(methylcarbonyloxy)-5-(tert.butyldimethylsilyloxy)cyclohexylacetate: (4,
1.07 parts;
3-hydroxy-5-(tert.butyldimethylsilyloxy)-(lS,3R,5R)-cyclohexylacetate: (5, 2.8 parts,
70% based on recovered starting material).
1H NMR (CDC13): δ 0.06 (s, 9H), 0.87 (s, 6H), 1.35-1.60, (m, 3H), 2.06 (s, 3H), 2.15 (m, 3H), 3.7 (m, 2H), 4.75 (m, 1H)
13C NMR (CDCl3): δ -4.60, 18.15,21.38, 25.90, 39.98,40.31,43.93, 65.45, 66.40, 68.17, 170.68
IR(CHC13): 758.43, 838.93, 1049.42, 1109.15, 1218.09, 1254.01, 1370.09, 1725.03, 2859.8,2887.95, 2952.33, 3017.48
Mass: Base m/e = 75 other m/e: 231, 171, 129, 117, 105, 97, 79, 75, 67, 59
Elemental analysis: calculated for C14H28O4Si: C 58.33%, H 9.72%
Found : C 58.15%, H 10.20% Specific rotation [α]D = - 4.8 (c 1, CHC13) e.e. >95%
Example 4:
Preparation of 3-oxo-5-(tert.butyIdimethylsilyloxy)-(1S', 5S)-cyclohexylacetate (6)
Cis,cis-3-(methylcarbonyloxy)-5-(tert.butyldimethylsilyloxy)-(1S,3R,5R)-cyclohexyl-
acetate (5, 1.40 parts, 2.78 mmol) was dissolved in dichloromethane 5 parts to the
solution sodium acetate (0.1 part) and pyridinium chlorochromate (1.57 parts, 7.3
mmol) were added. The mixture was stirred for 5 hr at RT. Residue was extracted
with ether (3x10 parts). Organic extracts were combined, filtered through ceilite.
Filtrate was washed with brine:water (1:1), finally with brine. Organic layer was dried
on anhydrous sodium sulphate and concentrated under vacuum. Residue was filtered
through silica gel column to afford 3-oxo-5-(/er/.butyldimethylsilyloxy)-(15, 55)-
cyclohexylacetate 6 (1.30 parts, 93.5%).
1H NMR (CDC13): δ 0.10 (d, 9H), 0.88 (d, 6H), 2.06 (s, 3H), 2.45 (m, 4H), 2.70 (m,2H), 4.00 (m, 1H), 5.00 (m, 1H)
13C NMR (CDCl3): δ -4.95, 17.82, 20.97, 25.57, 39.34, 45.93, 50.30, 65.98, 67.23, 169.87, 205.27
IR(CHC13): 442.57, 756.83, 1218.50, 1244.99, 1723.00, 2857.44, 2932.80, 2953.64, 3019.98
Mass: Base m/e = 163 other m/e: 185, 169, 145, 127, 117, 111, 101, 95, 75, 59
Elemental analysis: calculated for C14H26O4Si: C 58.74%, 9.09%
Found : C 58.60%, H 9.8%
Specific rotation [α]D = -11.54 (c 1, CHC13)

We claim :
1. A process for the preparation of a novel 3-oxo-5-(tert.butyldimethylsilyloxy)-
(1S,5S)-cyclohexylacetate having formula 6
(Formula Removed)
useful as an intermediate for ß-hydroxy -lactone which comprises extracting
3-hydroxy-5-(tert.butyldimethylsilyloxy)-(1S,3R,5R)-cyclohexylacetate having
formula 5 in an organic solvent with chlorochromate of tertiary amines at a temperature ranging from 10-30°C, quenching the above reaction by adding diethyl ether, filtering the mixture through ceilite and washing with brine, removing the solvent by evaporation, followed by fast column filtration to obtain 3-oxo-5-(tert.butyldimethylsilyloxy)-(1S,5S)-cyclohexylacetate.
2. A process as claimed in claim 1 wherein the organic solvent used for the reaction is selected from the group consisting of ethyl acetate, chloroform, dichloromethane.
3. A process for the preparation of a novel 3-oxo-5-(tert.butyldimethylsilyloxy)-(1S,5S)-cyclohexylacetate useful as an intermediate for ß-hydroxy δ-lactone useful as an intermediate for ß-hydroxy -lactone substantially as herein described with reference to the examples.

Documents:

0090-del-2001-abstract.pdf

0090-del-2001-claims.pdf

0090-del-2001-complete specification granted.pdf

0090-del-2001-correspondence-others.pdf

0090-del-2001-correspondence-po.pdf

0090-del-2001-description (complete).pdf

0090-del-2001-form-1.pdf

0090-del-2001-form-2.pdf

0090-del-2001-form-4.pdf

abstract.jpg

« Previous Patent

Next Patent »

Patent Number

199870

Indian Patent Application Number

0090/DEL/2001

PG Journal Number

36/2008

Publication Date

05-Sep-2008

Grant Date

05-Jan-2007

Date of Filing

31-Jan-2001

Name of Patentee

Council of Scientific and Industrial Research

Applicant Address

Rafi Marg, New Delhi

Inventors:

#	Inventor's Name	Inventor's Address
1	Sandeep Raghunath Ghorpade	National Chemical Laboratory, Pune 411008
2	Uttam Ramrao Kalkote	National Chemical Laboratory, Pune 411008
3	Subhash Prataprao Chavan	National Chemical Laboratory, Pune 411008
4	Sunil Ramchandra Bhide	National Chemical Laboratory, Pune 411008
5	Thottappillil Ravindranathan	National Chemical Laboratory, Pune 411008

PCT International Classification Number

A 61 K 31/120

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA