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The synthesis of [ 14 C]‐3S,4R‐4‐(4‐fluorophenyl)‐3‐(3,4‐methylenedioxyphenoxymethyl)piperidine hydrochloride (BRL 29060A), and mechanistic studies using carbon‐13 labelling
Author(s) -
Willcocks K.,
Barnes R. D.,
Rustidge D. C.,
Tidy D. J. D.
Publication year - 1993
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.2580330815
Subject(s) - chemistry , piperidine , enantiomer , labelling , stereochemistry , ring (chemistry) , yield (engineering) , hydrochloride , methylene , benzene , medicinal chemistry , organic chemistry , biochemistry , materials science , metallurgy
Paroxetine, BRL 29060A 1 has been labelled with both carbon‐14 and carbon‐13. Hydroxymethylation of 4‐(4‐fluorophenyl)‐1‐methyl‐1,2,5,6‐tetrahydropyridine, using [ 14 C]formaldehyde, produced an enantiomeric mixture of products which was taken without separation through a multistage sequence. Resolution of the mixture of stereoisomers at the penultimate step gave [ 14 C]BRL 29060A with the required configuration. The overall radiochemical yield was 8%. At some stage in this process, as shown by C‐13 labelling studies, scrambling of the label took place to give BRL 29060A with the majority of the label in the C‐2 position of the piperidine ring and the remainder at the expected 7‐methylene position. Further investigations of this route using carbon‐13 as the label are described. When sesamol, (3,4‐methylenedioxyphenol) was reacted with the O‐benzene sulphonate of (±)‐ cis ‐4‐(4‐fluorophenyl)‐3‐(hydroxy[ 13 C]methyl)‐l‐methylpiperidine, an inversion of configuration resulted via the previously described 1‐aza[3.1.1]bicycloheptane ring system. It is also shown that the corresponding (±)‐ trans ‐substituted piperidine, under similar conditions, does not undergo this inversion.