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

Article abstract of DOI:10.1002/1099-1344(200006)43:7<683::AID-JLCR353>3.0.CO;2-D

(-)OSU-6162, ((S)-(-)-3-[3-(methylsulfonyl)phenyl]-1-propylpiperidine hydrochloride), 1, is a 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-propylpiperidinc-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).