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

<jats:title>Abstract</jats:title><jats:p>2′Amino‐4′‐fluoro‐4‐[4‐hydroxy‐4‐(3‐trifluoromemethylphenyl)‐piperidino]butyrophenone (ID‐470B)(<jats:bold>1</jats:bold>), 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‐<jats:sup>14</jats:sup>C) (<jats:bold><jats:italic>2a</jats:italic></jats:bold>) was prepared from cyclopropane‐carboxylic‐<jats:sup>14</jats:sup>c acid by the Friedel‐Crafts reaction with m‐difluoro‐benzene. Ring‐opening of <jats:bold><jats:italic>2a</jats:italic></jats:bold> with hydrogen chloride gave 4‐chloro‐2′,4′‐difluorobutyrophenone‐1‐<jats:sup>14</jats:sup>c (<jats:bold><jats:italic>3a</jats:italic></jats:bold>). After ketalization of <jats:bold><jats:italic>3a</jats:italic></jats:bold>, the resulted ketal (<jats:bold>4</jats:bold>) was condensed with the piperidine (<jats:bold>5</jats:bold>) and subsequently hydrolyzed with hydrochloric acid to give <jats:bold>6</jats:bold>. Benzylamination of <jats:bold>6</jats:bold>. with benzylamine, followed by debenzylation by catalytic hydrogenolysis gave ID‐4708‐(carbonyl‐<jats:sup>14</jats:sup>C) (<jats:bold>1</jats:bold>). The overall radiochemical yield of <jats:bold>1</jats:bold> from barium carbonate‐<jats:sup>14</jats:sup>C was 13%.</jats:p>