PROCESS FOR THE PREPARATION OF KETIMINES

摘要

Described is a process for the preparation of compounds of formula (1a) which comprises reacting an isomeric mixture consisting of from 75 to 95 % of compound of formula (2a) and from 5 to 25 % of a compound of formula (2b) with methylamine, in a suitable solvent, to form a sertraline-imine isomeric mixture consisting of from 75 to 95 % of formula (1a) and from 5 to 25 % of formula (1b)(A1), or reacting an isomeric mixture consisting of from 75 to 95 % of a compound of formula (2a) and from 5 to 25 % of a compound of formula (2b) with methylamine, in a suitable solvent, using suitable methods of isolation to form an enriched sertraline-imine isomeric mixture, consisting of > 99 % of a compound of formula (1a) and < 1 % of a compound of formula (1b)(A2); and then subjecting the sertraline-imine isomeric mixture obtained according to reaction route (A1) or (A2), in a suitable solvent, to recrystallisation (B), in accordance with scheme (I) wherein in formula (1a), R1, R2 and R3 are each independently of the others hydrogen, halogen, trifluoromethyl or C1-C4alkoxy and formulae (1b), (2a) and (2b) are as defined in the description.