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Improved synthesis of stable isotope labeled and carbon‐14 labeled (S)‐(−)‐3‐[3‐(methylsulfonyl) phenyl]‐1‐propylpiperidine hydrochloride; (−)‐OSU‐6162
Author(s) -
Chaudhary Ashok G.,
McGrath James P.
Publication year - 2000
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 - 10.1002/1099-1344(200006)43:7<683::aid-jlcr353>3.0.co;2-d
Subject(s) - chemistry , methyl iodide , hydrochloride , iodide , sulfide , sulfone , yield (engineering) , alkylation , carbon 14 , organic chemistry , medicinal chemistry , radiochemistry , catalysis , materials science , metallurgy , physics , quantum mechanics
(−)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 [ 13 C, 2 H 3 ]methyl iodide or [ 14 C]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.