Improved synthesis of stable isotope labeled and carbon-14 labeled (S)-(−)-3-[3-(methylsulfonyl) phenyl]-1-propylpiperidine hydrochloride; (−)-OSU-6162

(−)OSU-6162, ((S)-(−)-3-[3-(methylsulfonyl)phenyl]-1-propylpiperidine hydrochloride), 1, it is dopamine autoreceptor antagonist with potential atypical antipsychotic properties. The synthesis of stable labeled and carbon-14 labeled (−)-OSU-6162 was achieved by an alkylation of the anion of (S)-3-(1-propylpiperdine-3-yl)-benzenethiol, 5, with either [13C, 2H3]methyl iodide or [14C]methyl iodide to provide the corresponding methyl sulfide. Selective oxidation of the methyl sulfide to the sulfone and conversion to its hydrochloride salt gave either stable isotope labeled (−)-OSU-6162 or carbon-14 labeled (−)-OSU-6162. The overall radiochemical yield was 36% with chemical and radiochemical purity exceeding 99% by HPLC analysis. The precursor thiol (5) was provided by a modified synthetic route from commercially available (S)-(−)-3-(3-(hydroxyphenyl)-1-propylpiperidine); ((S)-(−)-PPP), 2, in three steps via the triisopropylsilanethiolate intermediate (7). Copyright © 2000 John Wiley & Sons, Ltd.