反应详情

To a stirred solution of (3S)-3-amino-pyrrolidine-1-carboxylic acid, benzyl ester (4.40 g, 20 mmol) in methanol (120 mL) was added cyclohexanone (2.75 g, 28 mmol) followed by sodium cyanoborohydride (1.50 g, 24 mmol) at room temprerature. After 3 h, the reaction mixture was concentrated, diluted with dichloromethane (200 mL), washed with aqueous sodium bicarbonate (100 mL), 1 N sodium hydroxide (50 mL), brine (50 mL) and dried (Na2SO4). The crude was purified by flash chromatography using 5% methanol in dichloromethane to give (3S)-3-cyclohexylamino-pyrrolidine-1-carboxylic acid benzyl ester in 73% yield. 1H NMR (300 MHz, CDCl3): in δ 7.36–7.26 (m, 5H), 5.11 (s, 2H), 3.65–3.35 (m, 4H), 3.1–2.95 (m, 1H), 2.5–2.38 (m, 1H), 2.11–1.98 (m, 1H), 1.92–1.54 (m, 5H), 1.31–0.95 (m, 6H); 13C NMR (300 MHz, CDCl3): in δ 154.9, 137.1, 128.4, 127.8, 66.7, 55.0, 54.6, 53.8, 52.6, 44.7, 44.3, 34.1, 32.8, 32.0, 26.1, 25.1; MS (ESI+), 303 (M+H); Rf=1.16.

1. concentrationthe reaction mixture was concentrated
2. additiondiluted with dichloromethane (200 mL)
3. washwashed with aqueous sodium bicarbonate (100 mL), 1 N sodium hydroxide (50 mL), brine (50 mL)
4. dry with materialdried (Na2SO4)
5. customThe crude was purified by flash chromatography