Patent ID: 7199257

Claim:
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 R—SO 2 —X 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 (I) an inorganic peroxy salt in a mixture of water and a solvent miscible or not miscible with water, in the latter case in the presence of a phase transfer catalyst, or (ii) aqueous hydrogen peroxide A) in a C I –C 4 aliphatic carboxylic acid, or B) under aqueous basic conditions, in the presence of an organic solvent miscible with water, or C) in an organic solvent not miscible with water in the presence of a phase transfer catalyst and a salt of a metal belonging to the vanadium or chromium group to obtain the compound of the Formula (I), (Ia) or (Ib).