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(3R,4S)-4-(4-Fluorophenyl)-3-hydroxymethyl-1-methylpiperidine: conformation and structure monitoring by vibrational circular dichroism.

Authors
Type
Published Article
Journal
The Journal of organic chemistry
Publication Date
Volume
67
Issue
1
Pages
161–168
Identifiers
PMID: 11777454
Source
Medline
License
Unknown

Abstract

Absorption and vibrational circular dichroism (VCD) spectra of the title compound, a common intermediate in synthesis of many pharmaceuticals, were measured and analyzed in order to determine its absolute configuration and prevailing conformations. The analysis was combined with a systematic conformer search based on relative energies as well as with comparison of experimental and computed NMR shifts. The spectra were interpreted on the basis of ab initio simulations. The results indicate that the compound adopts exclusively a chair conformation of the piperidine ring with all the fluorophenyl, hydroxymethyl, and methyl substituents attached in equatorial positions. A limited rotation of the hydroxymethyl group is most consistent with the observed VCD pattern. VCD parameters were found significantly more sensitive to conformational changes than absorption or NMR. Concentration dependence of the absorption spectra indicated aggregation in concentrated solutions, but involved hydrogen bonds probably do not influence molecular conformation.

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