Racemization of optically active 2-substituted phenyl glycine esters
AssigneeUSV Limited
InventorsKrishna K. Maheshwari, Rayaprolu Kodandarama Sarma, Shreerang Vidyadhar Joshi, Anup Ramkrishna Barde, Rajiv Pandurang Sutar, Prasad Vasudeo Ranade
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Abstract
A process for preparing racemic mixtures containing nearly equal amounts of stereo isomers of compounds of formula (I), or their salts, by heating an enantiomerically enriched material with thionyl chloride. 1 A required useful enantiomer may thereby be recovered from unwanted mother liquors that would otherwise be otherwise be discarded.
Claims19
A process for preparing a racemic mixture containing substantially equimolecular amounts of enantiomers of the compound represented by structure (I):
- 5
A process of racemization to recover enantiomers from unwanted mother liquors, comprising:
- (a) liberating 2-(2-chlorophenyl) glycinate methyl ester as a free base from a concentrated R-enantiomer enriched mother liquor, that contains at least one of a tartarate or D-camphorsulfonate salt of an unwanted enantiomer;
- and
- (b) heating the free base with thionyl chloride so as to effect racemization to form racemized ester hydrochloride.
A process for preparing a racemic mixture containing substantially equimolecular amounts of enantiomers of the compound represented by the structure (I) below or a salt thereof:
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- wherein preparation of the racemic mixture is carried out by heating an optically active mixture with thionyl chloride to effect racemization.
A process of racemization of an optically active mixture of compounds comprising the steps of:
- (a) breaking up a tartarate mixture so as to obtain a substantially pure free amino ester;
- and
- (b) contacting the substantially pure free ester with thionyl chloride so as to effect racemization.
The process of liberating free (−) enriched 2-(2-chlorophenyl) glycine methyl ester free base from its tartaric acid salt comprising the steps of:
- (a) providing (−) enriched methyl-2-(2-chlorophenyl) glycinate (+) tartaric acid salt of methyl-2-(2-chlorophenyl) glycinate in methanol;
- (b) adding approximately 10% sodium bicarbonate solution until a pH approximately within the range of 7.0-7.50 is attained;
- (c) allowing the reaction mixture to settle;
- (d) separating a bottom layer of methyl-2-(2-chlorophenyl) glycinate from the solution in step (c);
- (e) extracting an upper aqueous layer of the solution of step (c) with dichloromethane;
- (f) removing the dichloromethane layer of step (e) and combining said dichloromethane layer with the methyl-2(2-chlorophenyl) glycinate layer;
- and
- (g) drying the mixed layers of step (f) over anhydrous sodium sulfate and dichloromethane distillation at atmospheric temperature.
The process of racemization of methyl-2-(2-chlorophenyl) glycinate comprising the steps of:
- (a) providing a solution of methyl-2-(2-chlorophenyl) glycinate dissolved in methanol;
- (b) cooling the mixture of step (a) to approximately 5° C. by chilling with at least one of a circulating water or a brine;
- (c) adding thionyl chloride to the cooled mixture of step (b) while maintaining a temperature of the mixture between approximately 25° C. and 30° C.;
- (d) heating the mixture of step (c);
- (e) distilling out the methanol from the heated mixture of step (d) while maintaining a temperature of the mixture below approximately 60° C.;
- (f) cooling the reaction mixture of step (e);
- (g) adding water to the mixture of step (f) while stirring until a substantially clear solution is obtained;
- (h) cooling the mixture of step (g) to approximately 10° C.;
- (i) adding an approximate 47% solution of caustic to the mixture of step (g) until a pH between approximate 7.0-7.5 is obtained;
- and
- (j) allowing the mixture of step (i) to settle and separating (±)-methyl-2-(2-chlorophenyl) glycinate.
The process of converting methyl-2-(2-chlorophenyl) glycinate to a tartaric acid salt of methyl-2-(2-chlorophenyl) glycinate comprising the steps of:
- (a) dissolving tartaric acid in methanol;
- (b) dissolving methyl-2-(2-chlorophenyl) glycinate in methanol;
- (c) adding the mixture of step (b) to the mixture of step (a);
- (d) stirring the mixture of step (c);
- (e) adding tartaric acid salt of methyl-2-(2-chlorophenyl) glycinate to seed the mixture of step (d);
- and
- (f) separating the solution of step (e) into crystals of tartaric acid salt of methyl-2-(2-chlorophenyl) glycinate and a mother liquor.
The process of isolating (−)-methyl-2-(2-chlorophenyl) glycinate comprising the steps of:
- (a) Providing a solid mass containing a hemitartate of methyl-2-(2-chlorophenyl) glycinate;
- (b) dissolving the mass of step (a) in water;
- (c) adding approximately 40% caustic lye to the solution of step (b) until a pH approximately within the range of 7.0-7.5 is obtained;
- (d) allowing the mixture of step (c) to settle;
- (e) separating a layer of methyl-2-(2-chlorophenyl) glycinate from the mixture of step (d) to yield a reactive solution;
- (f) adding dichloromethane to the reactive solution of step (e);
- (g) separating a lower dichloromethane layer from the mixture of step (f) to yield a reactive product;
- (h) combining the separated dichloromethane layer of step (g) with the reactive product of step (e);
- and
- (i) drying the product of step (h) over anhydrous sodium sulfate and dichloromethane distillation at atmospheric pressure.
The process of isolating a resolved ester comprising the steps of:
- (a) dissolving a (+) tartaric acid salt of methyl 2chlorophenyl glycinate in water;
- (b) adding approximately 10% sodium bicarbonate solution to the solution of step (a) until a pH within the range of 7.0-7.5 is obtained;
- (c) allowing the mixture of step (b) to settle;
- (d) separating a layer of methyl-2-(2-chlorophenyl) glycinate and charging the aqueous layer of step (c) with an effective amount of dichloromethane;
- (e) stirring the aqueous layer of step (d) after charging dichloromethane;
- (f) separating a dichloromethane extract layer from the solution of step (e);
- (g) combining the dichloromethane extract layer of step
- (f) with (+)-methyl-2-(2-chlorophenyl) glycinate to yield a mixture;
- (h) drying the mixture of step (g) over anhydrous sodium sulfate;
- and
- (i) recovering dichloromethane under vacuum.
Dependencies are inferred from the claim text.