Claims
- 1. A method for enhancing the solubility of a racemic mixture containing the dextro and levo isomers of 5-isopropyl-3-methyl-2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate which comprises:
- (a) subjecting racemic methyl 5-carboxy-2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate to an optical resolution to give (+)-methyl 5-carboxy-2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate; and
- (b) subjecting (+)-methyl 5-carboxy-2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate or activated form thereof to an esterification reaction to give (+)-5-isopropyl 3-methyl 2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.
- 2. The method of claim 1, which comprises
- (a) reacting racemic methyl 5-carboxy-2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate with cinchonidine to give a diastereoisomeric salt of (-)-methyl 5-carboxy-2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate and a diastereoisomeric salt of (+)-methyl 5-carboxy-2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate, and further removing some of the diastereoisomeric salt of (-)-methyl 5-carboxy-2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate, which is precipitated during the reaction;
- (b) neutralizing the product obtained in the above step (a) by an acid to give a mixture of (-)-methyl 5-carboxy-2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate and (+)-methyl 5-carboxy-2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate;
- (c) reacting the products obtained in the above step (b) with cinchonine and then removing precipitated diastereoisomeric salt of (-)-methyl 5-carboxy-2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate to give diastereoisomeric salt of (+)-methyl 5-carboxy-2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate;
- (d) neutralizing the product obtained in the above step (c) by an acid to give (+)-methyl 5-carboxy-2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate; and
- (e) reacting the product obtained in the above step (d) or its activated form with isopropyl alcohol to give (+)-5-isopropyl 3-methyl 2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.
Parent Case Info
This application is a continuation of application Ser. No. 07/090,091, filed on Aug. 27, 1987, now abandoned.
This invention relates to novel (+)-5-isopropyl 3-methyl 2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.
US Referenced Citations (2)
Non-Patent Literature Citations (2)
Entry |
Jacques et al., Enantiomers, Racemates, And Resolutions, pp. 251-263 Wiley-Interscience Publishers (1981). |
Jacques et al., Enantiomers, Racemates and Resolutions, pp. 251-263, Wiley-Interscience publishers 1983. |
Continuations (1)
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Number |
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90091 |
Aug 1987 |
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