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An enantioselective synthesis of S ‐γ‐[(4‐trifluoromethyl)phenoxy]benzenepropanamine‐[3‐ 14 C] hydrochloride, an important metabolite of fluoxetine hydrochloride
Author(s) -
Wheeler William J.
Publication year - 1992
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.2580310608
Subject(s) - chemistry , enantioselective synthesis , hydrochloride , cyanohydrin , trifluoromethyl , acetophenone , enantiomer , borane , stereochemistry , metabolite , yield (engineering) , medicinal chemistry , organic chemistry , catalysis , biochemistry , alkyl , materials science , metallurgy
The S ‐enantiomer of γ‐[(4‐trifluoromethyl)phenoxy]benzenepropanamine‐[3‐ 14 C] hydrochloride has been prepared in eight steps from acetophenone‐[carbonyl‐ 14 C]. The key step in the synthesis involved the enantioselective reduction of R ‐2‐chloroacetophenone‐[1‐ 14 C] with (‐)‐diisopinocampheylchloroborane in an 86.5% yield. The chlorohydrin was converted to R ‐phenyloxirane‐[1‐ 14 C], which was subsequently converted to the corresponding R ‐cyanohydrin by reaction with TMS‐CN/CaO. Borane reduction and arylation, followed by salt formation yielded S ‐γ‐[(4‐trifluoromethyl)phenoxy]benzenepropanamine‐[3‐ 14 C] hydrochloride.