Process for the enantioselective synthesis of 2(R)-benzylsuccinic acid monoamide derivatives

摘要

Two processes are described for the preparation of the optically pure compounds of formula 1: <IMAGE> (1) in which R1 and R2 are e.g. alkyl, R3 and R4 are e.g. hydrogen and R5 is e.g. hydrogen. Both processes include, as key steps, the enantioselective hydrogenation of a C=C double bond and the regioselective formation of a dicarboxylic acid monoamide derivative. In one process a phenylitaconic acid derivative is asymmetrically hydrogenated to give an optically active (R)-benzylsuccinic acid which is then converted to a diester, said diester being converted to the monoamide compound of formula 1. In the second process, a phenylitaconic acid derivative is converted to its anhydride, and the anhydride is then converted to a monoamide which is then asymmetrically hydrogenated to give the compound of formula 1.