Patent ID: 7199257
Filing Date: 2007-04-03
Classification: C07C,C07D

Abstract:
1. A process for the synthesis of racemic or optically pure R-(−)- and S-(+)-N-[4-cyano-3-trifluoro methyl-phenyl]-3-[4-fluorophenyl-sulfonyl]-2-hydroxy-2-methylpropionamide of formula (I), (Ia) and (Ib), respectively, which comprises the steps of: (a) reacting racemic or optically pure 2,3-dihydroxy-2-methyl-propionic acid of formula (VII) with thionyl chloride in a halogenated hydrocarbon or in an aromatic solvent in the presence of an aromatic amine as base to obtain a compound of the Formula (VI) (b) reacting the obtained racemic or optically pure 4-chloro-carbonyl-4-methyl-1,3,2-dioxathiolane-2-one of the Formula (VI) with 4-cyano-3-trifluoromethyl-aniline in an inert solvent in the presence of a tertiary amine as base between −40 and 0° C. to obtain racemic or optically pure 4-{[4-cyano-3-(trifluoromethyl)-anilino]-carbonyl}-4-methyl-1,3,2-dioxathiolane-2-one of formula (V) (c) hydrolyzing the obtained racemic or optically pure 4-{[4-cyano-3-(trifluoromethyl)-anilino]-carbonyl}-4-methyl-1,3,2-dioxathiolane-2-one of formula (V) under aqueous basic conditions to obtain racemic or optically pure N[4-cyano-3-(trifluoromethyl)-phenyl]-2,3-dihydroxy-2-methyl-propionamide of formula (IV) (d) sulfonylating the formed racemic or optically pure N-[4-cyano-3-(trifluoromethyl)-phenyl]-2,3-dihydroxy-2-methyl-propionamide of formula (IV) with a sulfonyl halogenide of formula wherein the meaning of R is methyl, p-tolyl or p-bromo-phenyl and X is a halogen atom—in a halogenated hydrocarbon as solvent in the presence of a tertiary amine as base to obtain a compound of the Formula (III) (e) reacting the obtained racemic or optically pure compound of the Formula (III) wherein R is methyl, p-tolyl or p-bromo-phenyl with 4-fluorothiophenol in the presence of a base, to obtain a racmic or optically active thioether compound of the Formula (II) and (f) finally oxidizing the obtained racemic or optically pure thioether of the Formula (II) with