Benzylamine → (S)-1-benzyl-3-(p-toluenesulfonylamino)pyrrolidine

Participants

Reaction Steps

(S)-2-(2'-Methanesulfonyloxyethyl)-1-(p-toluenesulfonyl)aziridine, 3, (54.5 g) was dissolved in warm tetrahydrofuran (50 mL) and the solution added dropwise over 20 minutes to a solution of benzylamine (40 g) and triethylamine (40 g) in dimethyl sulfoxide (250 mL) at 75° to 85° C. The resulting solution was heated another 2.5 hours at 75° to 85° C. and then concentrated under vacuum to remove tetrahydrofuran and dimethyl sulfoxide. The residue was dissolved in toluene (300 mL) and cautiously treated with 10 g of dry ice followed by 1.0N NaOH (150 mL). The layers were separated and the toluene layer treated cautiously with more dry ice (3 g) followed by 20 mL 1.0N NaOH. This carbon dioxide--NaOH extraction procedure was repeated three more times and the resulting toluene solution concentrated under vacuum to give (S)-1-benzyl-3-(p-toluenesulfonylamino)pyrrolidine, 4, as an amber oil. The oil was dissolved in warm (60° -70° C.) toluene (15 mL) and a solution (30 mL) of isopropyl alcohol saturated with hydrogen chloride gas was added. The solution was stirred and cooled to -5° C. where it was maintained for 3 hours. The solid product was collected and washed with isopropyl alcohol and ether and vacuum dried to give (S)-1-benzyl-3-(p-toluenesulfonylamino)pyrrolidine hydrochloride as an off-white solid (46.5 g, 74% combined yield for Steps 3 and 4). A portion was recrystallized from isopropyl alcohol: mp 179°-181° C.

Provenance & Evidence