Enantiomeric enrichment of (+)-(3R,4S)-4-(4-fluorophenyl)-3-hydroxymethyl-1-methylpiperidine by crystallization.

ABSTRACT

Two-fold crystallization of trans-4-(4-fluorophenyl)-3-hydroxymethyl-1-methylpiperidine enriched in (+)-enantiomer 3b (65.2-79.4% ee) yielded the racemate that crystallized out of solution and the mother liquor highly enriched in 3b (95.4-97.6% ee). Differences in infrared spectra of the racemate and enantiomer proved that the racemate consists of a racemic compound. Furthermore, solution NMR spectra of enriched 3b showed differentiation of some resonances (self-induced non-equivalence), which indicated strong diastereomeric interactions between solutes in apolar solvent. The enantiomeric composition of products was determined by NMR spectroscopy in the presence of R-Mosher acid.