A Low-Waste Process To Sertraline By Diastereomeric Crystal Resolution and Waste Isomer Racemisation

A semi-continuous method for recovering waste sertraline isomers from a diastereomeric crystallisation process is described in which the mother liquors from a highly selective mandelic acid resolution for the (1S,4S) isomer are treated sequentially with SCRAM, an iridium-based chiral amine racemisation catalyst, and then catalytic potassium tertiary butoxide to epimerise the methine chiral centre. The green, low-waste process also deals with recovery and recycle of the precious-metal catalyst, providing both good economics and high-quality product.