Reaction Steps
To a stirred solution of (2S*,3S*,5S*)-3-amino-1-benzyloxycarbonyl-5-methoxycarbonyl-2-phenylpiperidine (0.79 g, 2.16 mmol) and 2-methoxy-5-trifluoromethoxybenzaldehyde (0.59 g, 2.70 mmol) in CH2Cl2 (25.0 ml) was added NaB(OAc)3H (0.69 g, 3.24 mmol) potionwise at room temperature. The turbid reaction mixture was stirred at room temperature for 3 hours; the NaB(OAc)3H added dissolved gradually with stirring, and the turbidity of the reaction mixture decreased. sat. Na2CO3 aq. solution was added, and from the mixture was separated the CH2C2 layer. The aqueous layer was extracted with CH2Cl2. The combined CH2Cl2 layer and extracts were dried (Na2SO4), and concentrated in vacuo to give a pale yellow oil (1.55 g). This was flash chromatographed over SiO2 (Merck Kieselgel 60, 32.0 g). Elution with CH2Cl2 --MeOH (300:1/200:1) gave title compound (1.15 g, 93.1%) as a colorless syrup, which crystallized spontaneously on standing in a refrigerator. This was recrystallized from (i-Pr)2O to give analytically pure title compound (1.058 g, 85.3%). mp 93.5-95.0 C. (fine colorless needles); IRmax (nujol): 1730(s), 1700(s), 1610(w), 1498(s), 1220(s), 1147(s), 1110(s), 1080(s), 1055(s), 1028(s), 742(s), 730(s), 703(s), 695(s) cm-1 ; 1H-NMR δ: 7.43-7.23(m, 9H), 7.21(br.s, 1H), 7.09-7.00(m, 2H), 6.73(d, J=9.2 Hz, 1H), 5.39(br.d, J=5.3 Hz, 1H), 5.16(d, J=12.5 Hz, 1H), 5.02(d, J=12.5 Hz, 1H), 4.50(dd, J=13.7, 1.8 Hz, 1H), 3.79(d, J=13.9 Hz, 1H), 3.68(d, J=13.9 Hz, 1H), 3.63(s, 3H), 3.54(dd, J=13.7, 5.5 Hz, 1H), 3.28(ddd, J=10.2, 5.5 4.8 Hz, 1H), 2.89-2.28(m, 1H), 2.24-2.01(m, 1H), 1.54(br.s, 2H) ppm.
