Reaction Steps
(A mixture of two diastereomers and their enantiomers.) To 6-Methyl-2-phenyl-piperidine-3-carboxylic acid methyl ester (1.63 g, 7.0 mmol) in 20 mL of 10% aqueous NaHCO3 at 0° C. was added benzylchloroformate (1.25 g, 7.35 mmol). The mixture was stirred for 45 minutes at 0° C., and was then warmed to room temperature and stirred for an additional 30 minutes. The mixture was partitioned with ether, and the organic phase was dried over MgSO4 and concentrated. Silica gel chromatography (9:1 hexanes/EtOAc) gave 1.62 g (63%) of the title compound as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.1–7.4 (comp, 20H, both diastereomers), 6.1 (br, 1H, minor diastereomer), 5.74 (d, J=3.6, 1H, major diastereomer), 5.05–5.26 (comp, 8H, both diastereomers), 4.67 (d, J=6.0 Hz, 1H, major diastereomer), 4.57 (m, 1H, minor diastereomer), 4.10–4.20 (m, 2H, major diastereomer), 3.70 (s, 3H, major diastereomer), 3.59 (s, 3H, major diastereomer), 3.29 (app dt, J=4.5, 9.4 Hz, 1H, major diastereomer), 2.85 (m, 1H, minor diastereomer), 2.27 (app dq, J=4.1, 13.7 Hz, minor diastereomer), 1.85–2.15 (comp, 4H, both diastereomers), 1.55–1.80 (comp, 3H, both diastereomers), 1.34 (d, J=6.8 Hz, 3H, major diastereomer), 0.37 (d, J=7.1 Hz, 3H, minor diastereomer); 13C NMR (100 MHz) δ 172.8, 140.0, 136.7, 128.5, 128.4, 128.2, 128.0, 127.8, 127.7, 127.6, 127.2, 127.1, 127.0, 126.9, 126.4, 67.5, 66.9, 65.3, 56.4, 52.0, 47.5, 46.6, 44.3, 42.6, 30.2, 25.6, 22.1, 19.8, 17.2, 16.0; mass spectrum m/e calcd. for M+H=368.2. Found 368.2, 324.2 (base).
