Protopine hydrochloride.

Protopine hydrochloride (5,6,14,14a-tetrahydro-14a-hydroxy-7-methyl-8H-bis[1,3]benzodioxolo[5,6-a:4,5-g]quinolizinium chloride, C20H20NO5(+)-Cl(-)) is the salt of the isoquinoline alkaloid protopine. It is formed by the action of dilute hydrochloric acid on the protopine free base. The N-methyl and hydroxyl groups are in a trans configuration in the quinolizine ring and the central quinolizine N-C bond is unusually long [1.579 (2) A]. The crystal is a racemate.

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.