Patent ID: 6133454
Filing Date: 2000-10-17
Classification: A61P,C07D

Abstract:
A process for the industrial preparation of a substituted perhydroisoindole of formula (I): ##STR9## or a pharmaceutically- acceptable salt thereof, characterised in that dimethyl succinate is reacted with benzaldehyde in methanolic medium, to yield the diacid of formula (II): ##STR10## which, after heating in an aprotic medium in the presence of acetic anhydride, yields the anhydride of formula (III): ##STR11## which is reacted with the perhydroisoindole of formula (IV) in an aprotic solvent ##STR12## to yield the compound of formula (V): ##STR13## which is subjected to catalytic hydrogenation using as asymmetric hydrogenation catalyst the complex rhodium/(2S,4S)-N-butoxycarbonyl-4-diphenylphosphino-2-diphenylphosphino-m ethylpyrrolidine or Rh/(S,S) BPPM, in methanolic or methylene chloride medium, followed by conversion to a salt in the presence of an amine A selected from the group consisting of (R)-1-phenylethylamine, morpholine, N-methylmorpholine and cyclohexylamnine, to yield a compound of formula (VI): ##STR14## which: in a basic medium in the presence of a mineral salt yields an addition salt of the compound of formula (I), which is converted, if desired, into the corresponding acid, or,in an acidic medium yields the compound of formula (I), which is converted, if desired, into a pharmaceutically- acceptable addition salt.