反应详情

Following General Procedure A, a solution of 4-ethoxyaniline (0.48 g, 3.5 mmol) and (R)-3-(4-oxo-piperidin-1-yl)butyronitrile (0.49 g, 3.0 mmol) in CH2Cl2 (10 mL), was treated with glacial AcOH (3 drops) and NaBH(OAc)3 (0.93 g, 4.4 mmol), stirring for 16 h at room temperature. Saturated aqueous NaHCO3 solution (15 mL) and 1N NaOH (2 mL) was added and the phases were separated and the aqueous extracted with CH2Cl2 (2×15 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The crude material was then purified by flash column chromatography on silica gel (1:1 EtOAc/CH2Cl2) to afford (R)-3-[4-(4-ethoxy-phenylamino)-piperidin-1-yl]-butyronitrile as a pale brown solid (90%). 1H NMR (CDCl3) δ 1.20 (d, 3H, J=6.6 Hz), 1.37 (t, 2H, J=7.2 Hz), 1.39 (m, 2H), 2.05 (br d, 2H), 2.36 (m, 3H), 2.47 (m, 1H), 2.81 (m, 2H), 3.07 (sex, 1H, J=7.2 Hz), 3.28 (m, 2H), 3.96 (q, 2H, J=7.5 Hz), 6.55 (d, 2H, J=9.0 Hz), 6.76 (d, 2H, J=9.0 Hz).

1. customthe phases were separated
2. extractionthe aqueous extracted with CH2Cl2 (2×15 mL)
3. dry with materialThe combined organic extracts were dried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe crude material was then purified by flash column chromatography on silica gel (1:1 EtOAc/CH2Cl2)