METHOD OF PRODUCING LAKOSAMIDE Russian patent published in 2016 - IPC C07C231/12 C07C231/20 C07C237/06 C07C237/22 

FIELD: chemistry.

SUBSTANCE: invention relates to method of lakosamide synthesis, active ingredient, used for treating neuropathies. Method is implemented by (a) hydroxymethylation of compound of formula V to obtain compound of formula VI; (b) hydrolysis of compound of formula VI to obtain compound of formula (VII); (c) reaction of salt compound of formula VII with 2-(S)-chloro- mandelic acid (HX *) in organic solvent to produce mixture of diastereomers VIII; (d) separation of mixture of diastereomers VIII to produce salt IX; and (e) converting salt IX in lakosamide. Hydroxymethylation (a) is carried out by reacting compound of formula (V) with alkylating agent in presence of base, at temperature ranging from 20 °C to 40 °C. Hydrolysis (b) is performed in presence of inorganic acid, preferably hydrochloric acid. Separation (d) of mixture of diastereomers VIII is performed by precipitation from mixture of at least one aprotic organic solvent and at least one proton solvent. Step (e) is performed in presence of acidating agent, at least one organic solvent, preferably nonpolar solvent, optionally mixed with water. Invention also relates to intermediate compounds of formulas VIII and XI.

EFFECT: technical result is production of lakosamide due to separation of racemic mixture of lakosamide and enantiomer cleaning of R-enantiomer.

25 cl, 6 ex

(VI)

(V)

(VII)

(VIII)

(IX)