Resolution and absolute configuration of 1,2,3,5,6,10bβ-hexahydro-6α-phenylpyrrolo[2,1-α]isoquinoline (McN-4612-Z). A problem of determination of the enantiomeric purity for a tertiary amine

Details for the resolution of 1,2,3,5,6,10bβ-hexahydro-6α-phenylpyrrolo2,1-α]isoquinoline (1) , a potent antidepressant-like compound, into its enantiomers with di-p-toluoyltartaric acid ( 2) are reported. Enantio-merically-enriched R-(+)-2-phenylpyrrolidine was transformed into enantiomerically-enriched 1 to determine enantiomeric purity and absolute stereochemistry for the resolved amines 1 . Thus, we ascertain that samples of (+)- and (—)- 1 with an enantiomeric purity of ≥99% were prepared, and that bioactive (+)- 1 possesses the 6S,10bR absolute configuration. The enantiomeric purity of ≥99% was confirmed by 360-MHz ¹H nmr examination of 1:1 diastereomeric salts formed from 1 or (—)- 1 and (+)-Mosher's acid (MTPA). The maximal optical rotation reported (ref 8) for (+)- 3 (100% o.p.) was shown to correspond to 100% e.e.