Reaction Steps
To a stirred solution of (2S*,3S*,4S*,5R*)-3-amino-1-benzyloxycarbonyl-4-hydroxymethyl-5-methyl-2-phenylpyrrolidine (0.61 g, 1.79 mmol) in dry CH2Cl2 (14 ml) was added a solution of 5-isopropyl-2-methoxybenzaldehyde (0.40 g, 2.24 mmol) in dry CH2Cl2 (2 ml) at room temperature. To this was then added NaBH(OAc)3 (0.57 g, 2.69 mmol) portionwise at room temperature. The added NaBH(OAc)3 dissolved gradually with stirring at room temperature. After stirring for 3 hours at room temperature, the reaction mixture was basified to pH 10-11 with 10% NaOH aq. solution. The mixture was separated, and the aqueous layer was extracted with CH2Cl2 (×3). The combined CH2Cl2 solution was washed with sat. NaCl aq. solution (×1), dried (K2CO3), and concentrated in vacuo to give a yellow oil (1.34 g). This was chromatographed over SiO2 (Merck Kieselgel 60, 20 g). Elution with n-hexane-AcOEt (30:1) followed by CH2Cl2 --MeOH (400:1→200:1) gave title compound (0.70 g, 78%) as a viscous pale yellow oil: IRmax (film): 3330(s), 1700(s), 1610(m), 1500(s), 1250(s), 1110(s), 1030(s), 815(s), 770(s), 738(s), 700(s) cm- ; 1H-NMR δ: 7.45-7.16(m, 9H), 7.05(dd, J=8.4, 1.8 Hz, 1H), 7.02(br.s, 1H), 6.88(d, J=1.8 Hz, 1H), 6.71(d, J=8.4 Hz, 1H), 5.33-4.93(m, 3H), 3.97-3.65(m, 3H), 3.81(d, J=12.1 Hz, 1H), 3.72(d,J=12.1 Hz, 1H), 3.67(s, 3H), 3.53-3.35(m, 1H), 3.38(dd,J=11.5, 7.9 Hz), 2.79 (sep, J=7.0 Hz, 1H), 2.17-1.98(m, 1H), 1.56(br.s, 4H), 1.18(d, J=7.0 Hz, 6H) ppm.
