New highly selective process for the production of enantiomerically pure phenyl-substituted 1,4-dihydropyridine-3,5-dicarboxylic acid derivatives

摘要

2-Benzylidene-3-oxo-butyric acid malimide esters(II), enantiomerically pure aminocrotonic acid malimide esters (IIIa) and enantiomerically pure acetoacetic acid malimide esters (VI) are new. Benzylidene compounds of formula (II), enantiomerically pure aminocrotonic acid esters of formula (IIIa) and enantiomerically pure acetoacetic acid esters of formula (VI) are new. [Image] R2phenyl substituted by 1 or 2 of halo, CN, ethynyl, OCF3, SMe, NO2, CF3, 1-4C alkyl, 2-4C alkenyl, 2-4C alkynyl or 1-4C alkoxy; A : H or 1-8C alkyl; or phenyl or benzyl (both optionally substituted by 1-3 of OH, NO2, halo, CN, COOH, CF3, OCF3 or 1-6C alkoxy or by NR6R7 or SO2R8); R6, R7H, Ph or 1-5C alkyl; R81-4C alkyl or Ph. Independent claims are also included for: (1) the preparation of enatiomerically pure (II), (IIIa) and (VI); and (2) the preparation of diastereomeric 1,4-dihydropyridines of formula (IVa) or (IVb) by: (a) reacting enatiomerically pure (II) with aminocrotonic acid ester of formula Me-C(NH2)=CH-COOR1 (III) in a solvent, optionally in presence of base; or (b) reacting enatiomerically pure (IIIa) with benzylidene compound of formula R2-CH=C(COMe)-COOR1 (IIa) in a solvent, optionally in presence of base. [Image] R11-8C alkyl (optionally substituted by 1-6C alkoxy) or 3-7C cycloalkyl.