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Labelling of neuroleptic butyrophenones. 1. syntheses of haloperidol‐ 14 C and trifluperidol‐ 14 C
Author(s) -
Nakatsuka Iwao,
Kawahara Kazuo,
Kamada Takeshi,
Yoshitake Akira
Publication year - 1978
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.2580140117
Subject(s) - chemistry , butyrophenone , grignard reaction , hydrochloric acid , haloperidol , piperidine , fluorobenzene , medicinal chemistry , hydrogen chloride , ring (chemistry) , organic chemistry , reagent , dopamine , benzene , neuroscience , biology
Abstract 4‐[4‐(4‐Chlorophenyl)‐4‐hydroxypiperidino]‐4′‐fluorobutyrophenone (haloperidol) (I) and 4′‐fluoro‐4‐[4‐hydroxy‐4‐(3‐trifluoromethylphenyl) piperidino] butyrophenone (trifluperidol) (II), neuroleptic drugs, were labelled at the carbonyl position with carbon‐14 for the use of metabolic studies. The syntheses were achieved according to the reaction scheme shown in Fig. 1. Cyclopropionic‐1‐ 14 C acid (IV) was prepared from cyclopropyl bromide (III) by Grignard reaction with carbon‐ 14 C dioxide. Condensation of IV with fluorobenzene, followed by ring‐opening with hydrogen chloride, gave 4‐chloro‐4′‐fluorobutyrophenone‐1‐ 14 C (VI). After ketalization of VI, the ketal (VII) was condensed with corresponding piperidine derivatives (VIIIa and VIIIb) and subsequently hydrolized with hydrochloric acid to give haloperidol‐1‐ 14 C (I) and trifluperidol‐1‐ 14 C (II), respectively. The overall radiochemical yields of I and II from barium carbonate‐ 14 C were 31 and 27%, respectively.