Labelling of neuroleptic butyrophenones. II. Synthesis of 2' amino 4' fluoro 4 [4 hydroxy 4 (3 trifluoromethylphenyl)piperidino]butyrophenone (carbonyl 14C)

Article abstract of DOI:10.1002/jlcr.2580160306

2'-Amino-4'-fluoro-4-[4-hydroxy-4-(3-trifluoromethylphenyl)-piperidino]butyrophenone (1), a novel neuroleptic agent, was labelled with carbon-14 at the carbonyl position for use in metabolic studies. The synthesis was achieved according to the reaction scheme shown. Cyclopropyl 2,4-difluorophenyl ketone-(carbonyl-¹⁴C) (2a) was prepared from cyclopropane-carboxylic-¹⁴C acid by the Friedel-Crafts reaction with m-difluorobenzene. Ring-opening of 2a with hydrogen chloride gave 4-chloro-2',4'-difluorobutyrophenone-1-¹⁴C (3a). After ketalization of 3a, the resulted ketal was condensed with the piperidine and subsequently hydrolyzed with hydrochloric acid to give 6. Benzylamination of 6 with benzylamine, followed by debenzylation by catalytic hydrogenolysis gave ID-4708-(carbonyl-¹⁴C) (1). The overall radiochemical yield of 1 from barium carbonate-¹⁴C was 13%.