Enantiomeric enrichment of (+)-(3R,4S)-4-(4-fluorophenyl)-3-hydroxymethyl-1-methylpiperidine by crystallization.
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.
Navrátilová
H
H
Department of Organic Chemistry, Masaryk University, Brno, Czech Republic. hanavra@chemi.muni.cz
Potácek
M
M
D003460:Crystallization; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D017374:Paroxetine / Q000138:chemical synthesis; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis; D013237:Stereoisomerism
D017374:Paroxetine; D010880:Piperidines; D017367:Selective Serotonin Reuptake Inhibitors; C453539:4-(4-fluorophenyl)-3-hydroxymethyl-1-methylpiperidine; C010655:femoxetine