Process for the preparation of lacosamide

摘要

A novel process for the synthesis of Lacosamide using D,L-serine as starting material is described, where the methylation reaction of hydroxyl is carried out using an inexpensive base such as NaOH and an inexpensive alkylating agent, non-toxic and non-carcinogenic, such as methyl p-toluenesulfonate; the R enantiomer is isolated from the racemic mixture of Lacosamide after selective hydrolysis of the acetamide, salification of the racemic mixture with a chiral acid (HX*) in an organic solvent, resolution of the diastereoisomeric mixture, preferably by precipitation of the R enantiomer, and subsequent acetylation of the optically pure intermediate.

主权项

1. A process for the synthesis of Lacosamide comprising the following steps:
(a) hydroxymethylation of a compound of formula V to obtain a compound of formula VI (b) hydrolysis of the compound of formula VI to obtain a compound of formula VII (c) salification of the compound of formula VII with a chiral acid (HX*) in an organic solvent, to obtain a diastereoisomeric mixture VIII (d) resolution of the diastereoisomeric mixture VIII to obtain a salt IX (e) conversion of the salt IX into Lacosamide.