Reaction Steps
(A mixture of two diastereomers and their enantiomers.). To ammonium chloride (1.18 g, 22.1 mmol) in 20 mL of benzene at 0° C. was added trimethylaluminum (22.1 mmol, 11.0 mL of a 2.0 M solution in toluene) The resultant mixture was stirred for 30 minutes at 0° C., and warmed to room temperature for an additional 30 minutes. To the mixture was then added 6-Methyl-2-phenyl-piperidine-1,3-dicarboxylic acid 1-benzyl ester 3-methyl ester as a solution in 20 mL of benzene, and the resultant mixture was heated to reflux for 6 hours. The reaction was then cooled to 0° C. and quenched carefully with 10 mL of 1 M HCl. The mixture was stirred for 30 minutes, filtered through celite, and the filter pad was rinsed with CH2Cl2. The filtrate was concentrated and the residue was dissolved in EtOAc, washed with saturated NaHCO3, dried over MgSO4 and concentrated. Silica gel chromatography (CHCl3 to eluted nonpolar material followed by 95:5 CHCl3/MeOH to elute the product) gave 560 mg (36%) of a mixture of the title compounds as a white foam. 1H NMR (400 MHz, CDCl3) δ 7.10–7.42 (comp, 20H, both diastereomers), 5.99 (d, J=5.1 Hz, 1H), 5.68–5.90 (br, 2H, both diastereomers), 5.67 (d, J=4.3 Hz, 1H), 5.00–5.26 (comp, 4H, both diastereomers), 4.53 (m, 1H), 4.17 (br, 1H), 3.15 (m, 1H), 2.75 (m, 1H), 2.28 (app dq, J=4.1, 13.2 Hz, 1H), 1.9–2.08 (m, 2H), 1.50–1.90 (comp, 5H), 1.34 (d, J=6.6 Hz, 3H), 0.68 (d, J=7.1 Hz, 3H); 13C NMR (100 MHz) δ 174.2, 128.6, 128.4, 128.3, 128.2, 128.1, 127.8, 127.6, 127.2, 127.1, 126.7, 67.6, 67.1, 56.9, 52.8, 47.4, 46.6, 30.2, 25.5, 22.3, 19.8, 16.3; Mass spectrum m/e calcd. for M+H=353.2. Found 353.0, 309.1, 219.0 (base).
