IMPROVED PROCESS OF AMIDE FORMATION

摘要

A process for the formation of 2-(methyloxy)-N-[2-methyl-1 -phenyl-2-(1 - pyrrolidinyl)propyl]-4,6-bis(trifluoromethyl)benzamide is disclosed, comprising treatment of 2,4-ditrifluoromethyl-6-methoxy-benzoic acid with an arylsulphonyl halide,C1-6alkylsulphonyl halide or di-C1-6alkylphosphoryl chloride, in the presence of a base and an aprotic solvent; followed by reaction with [2-methyl-1 -phenyl-2-(1 - pyrrolidinyl)propyl]amine or a salt thereof. Also disclosed is a process for the formation of [2-methyl-1-phenyl-2-(1- pyrrolidinyl)propyl]amine comprising: i) treatment of an a-haloketone with an alcohol in the presence of a base followed by reaction with pyrrolidine; ii) treatment of the product of stage i) with Ar-CH(R5)NH2 wherein R5 is C1-4alkyl and Ar is optionally substituted phenyl, followed by reduction with a sodium borohydride derivative; and iii) reduction of the product of stage ii) with hydrogen and a palladium catalyst. Also disclosed is the novel compound 2-pyrrolidinyl-2-methylpropiophenone or a salt or solvate thereof.