SYNTHESIS OF LOROETHYL)AMINOPHENYL]-3,3,4,4-TETRAFLUOROBUTANOIC ACID [3,3,4,4-TETRAFLUOROCHLORAMBUCIL]

Reaction of 2,2-dichloro-2-(4'-nitrophenyl) acetonitrile with mercury( II) oxide/pyridinium poly(hydrogen fluoride), (aqueous work-up), gave 2,2-difluoro-2-(4'-nitrophenyl)acetamide, from which were made the par ent acid and thence its acid chloride. This and ethyl propanedioate/me thyl lithium afforded ethyl 4,4-difluoro-4-(4'-nitrophenyl)-3-oxobutan oate, converted by SF4/HF into ethyl 3,3,4,4-tetrafluoro-4-(4'-nitroph enyl)butanoate. Catalytic hydrogenation of the nitro-group then gave t he 4'-amine, which was bis(hydroxyethylated) using oxirane. Conversion to the bis(chloroethyl) analogue utilized Ph3P/CCl4, whence acidic hy drolysis afforded loroethyl)aminophenyl]-3,3,4,3-tetrafluorobutanoic a cid. (C) 1998 Elsevier Science S.A. All rights reserved.