Patent ID: 8729308
Filing Date: 2014-05-20
Classification: C07B,C07C

Abstract:
1. A process for the synthesis of tapentadol comprising the following steps: a) reaction of a racemic mixture of compound (V) with a chiral acid in a polar solvent or mixture of polar solvents and subsequent precipitation of chiral salt (VI) b) treatment of the chiral salt (VI) with an aqueous base solution to obtain compound (VII) c) extraction with an organic solvent; d) reduction of the nitro group of the compound of formula (VII) to an amino group, to obtain a compound of formula (XII): e) conversion of the compound of formula (XII) into a compound of formula (XIV) by reaction with an organometallic reagent f) reaction of the compound (XIV) with an anhydride or a halide of an organic acid followed by hydrogenation to obtain, after hydrolysis, the compound of formula (X): g) the compound (X) is subjected to a diazotation reaction to obtain a diazonium salt of formula (XI): which is subjected to hydrolysis conditions to obtain tapentadol, wherein X is the anion resulting from the diazotation reaction that is carried out in an aqueous solution of a mineral acid selected from sulfuric acid, hydrochloric acid, phosphoric acid, methansulfonic acid, and trifluoroacetic acid, and wherein X*—is the anion resulting from the reaction with the chiral acid in step a) selected from D(−)mandelic acid, D(−)2-chloro mandelic acid, D(−)tartaric acid, and (2R,3R)—O,O′-dibenzoyl tartaric acid.