(R)-tert-Butyl 2-methylpiperidin-3-ylcarbamate (307) (8.2 g, 38 mmol) was suspended in a solution of DCM (500 mL) and DIEA (13.4 mL, 76.9 mmol). Benzyl chloroformate (6.6 mL, 46 mmol) was then added drop-wise over 5 minutes and the reaction was stirred at 0° C. for 30 minutes. Water was then added and the mixture was allowed to come to room temperature and stirred for 30 minutes. The organic phase was separated, washed with 1M HCl (aq), saturated NaHCO3 (aq), and brine. On TLC, the trans-isomer (309) displayed a higher silica Rf value than the cis isomer (308). The two diastereomers were separated by silica flash column chromatography (EtOAc/hexanes). The mixed fractions from the first purification were combined and subjected to a second purification. After two purifications, (2R,3R)-benzyl 3-(tert-butoxycarbonylamino)-2-methylpiperidine-1-carboxylate (308) (2.5 g, 7.2 mmol, 19% yield) and (2S,3R)-benzyl 3-(tert-butoxycarbonylamino)-2-methylpiperidine-1-carboxylate (309) (8 g, 23 mmol, 61% yield) were obtained.
