反应详情

Stir a solution of diisopropylethylamine (9.5 mL, 54.3 mmol), 6-chloronicotinonitrile (5 g, 36.2 mmol) and 3-tert-butyloxycarbonylpyrrolidine (10 g, 54.3 mmol) in DMF (10 mL). After 3 days, dilute with dichloromethane and an aqueous saturated solution of sodium bicarbonate and separate the layers. Extract the aqueous layer once with dichloromethane, dry (sodium sulfate), filter and concentrate. Filter through a plug of silica gel, wash with dichloromethane and concentrate to give [1-(5-cyanopyridin-2-yl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester as a white solid (8.13 g, 78%). 1H NMR (400 MHz, CDCl3) δ 8.38 (dd, 1H, J=2.4 Hz, 1.0 Hz), 7.58-7.55 (m, 1H), 6.33 (dd, 1H, J=9.8 Hz, 1.0 Hz), 4.85-4.7 (m, 1H), 4.40-4.25 (m, 1H), 3.85-3.30 (m, 4H), 2.35-2.25 (m, 1H), 2.08-1.90 (m, 1H), 1.43 (s, 9H); MS (ES): m/z=289 [M+H]+.

1. customan aqueous saturated solution of sodium bicarbonate and separate the layers
2. extractionExtract the aqueous layer once with dichloromethane
3. dry with materialdry (sodium sulfate)
4. filtrationfilter
5. concentrationconcentrate
6. filtrationFilter through a plug of silica gel
7. washwash with dichloromethane
8. concentrationconcentrate