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Labelling of neuroleptic butyrophenones. II. Synthesis of 2′amino‐4′‐fluoro‐4‐[4‐hydroxy‐4‐(3‐trifluoromethylpfenyl)piperidino]butyrophenone‐(carbonyl‐ 14 C)
Author(s) -
Nakatsuka Iwao,
Kawahara Kazuo,
Kamada Takeshi,
Yoshitake Akira
Publication year - 1979
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580160306
Subject(s) - chemistry , butyrophenone , benzylamine , cyclopropane , ketone , piperidine , medicinal chemistry , hydrogenolysis , organic chemistry , friedel–crafts reaction , carboxylic acid , ring (chemistry) , catalysis , neuroscience , dopamine , haloperidol , biology
2′Amino‐4′‐fluoro‐4‐[4‐hydroxy‐4‐(3‐trifluoromemethylphenyl)‐piperidino]butyrophenone (ID‐470B)( 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 in Fig. 1. Cyclopropyl 2,4‐difluorophenyl ketone‐(carbonyl‐ 14 C) ( 2a ) was prepared from cyclopropane‐carboxylic‐ 14 c acid by the Friedel‐Crafts reaction with m‐difluoro‐benzene. Ring‐opening of 2a with hydrogen chloride gave 4‐chloro‐2′,4′‐difluorobutyrophenone‐1‐ 14 c ( 3a ). After ketalization of 3a , the resulted ketal ( 4 ) was condensed with the piperidine ( 5 ) and subsequently hydrolyzed with hydrochloric acid to give 6 . Benzylamination of 6 . with benzylamine, followed by debenzylation by catalytic hydrogenolysis gave ID‐4708‐(carbonyl‐ 14 C) ( 1 ). The overall radiochemical yield of 1 from barium carbonate‐ 14 C was 13%.