Enantioseparation of paroxetine precursors by HPLC on amylose and tartardiamide-based chiral stationary phases

Two important precursors of antidepressant trans-(-)-paroxetine, i.e., trans-4-(4'-fluorophenyl)-3-hydroxymethyl-1-methylpiperidine and trans-3- ethoxycarbonyl-4-(4'-fluorophenyl)-1-methylpiperidine-2,6-dione have been directly separated by HPLC on Chiralpak AD-H and Kromasil CHI-TBB columns. All the experiments were conducted in the normal phase mode. The mobile phases were mixtures of n-hexane and alcohol modifiers including ethanol, 2-propanol, and 1-propanol, with or without addition of diethylamine. Excellent separation was obtained for both enantiomers. Effects of the type and content of polar alcohol modifiers on enantioseparation was investigated. An unusual retention behavior was observed, i.e., the retention of enantiomers increased when the alcohol modifier was changed from 2-propanol to ethanol. The elution orders of the enantiomers on both columns were examined. The thermodynamic parameters obtained from van't Hoff plots were all negative, which indicated that the chiral separation were enthalpically driven.