反应详情

温度

95 °C

0.24 g (1.35 mmol) of 5-bromo-2-fluoropyridine, 0.20 g (1.13 mmol) of 7-azaspiro[3.5]nonan-2-ol hydrochloride (JP 2003246780) and 0.51 g (3.94 mmol) of N,N-diisopropylethylamine in 3 mL of acetonitrile are placed in a sealed tube. 1 mL of DMF is added and the mixture is then heated at 95° C. for 12 hours. The reaction mixture is allowed to cool to room temperature and is then taken up in ethyl acetate and water. The aqueous phase is separated out and the combined organic phases are then washed with saturated aqueous ammonium chloride solution and dried over sodium sulfate, and the filtrate is concentrated under reduced pressure. After purification by chromatography on silica gel, eluting with a 95/5/0.5 mixture of dichloromethane, methanol and 28% aqueous ammonia, 0.138 g pure product is thus obtained in the form of a colourless gum.

1. temperatureto cool to room temperature
2. customThe aqueous phase is separated out
3. washthe combined organic phases are then washed with saturated aqueous ammonium chloride solution
4. dry with materialdried over sodium sulfate
5. concentrationthe filtrate is concentrated under reduced pressure
6. customAfter purification by chromatography on silica gel
7. washeluting with a 95/5/0.5 mixture of dichloromethane, methanol and 28% aqueous ammonia, 0.138 g pure product
8. customis thus obtained in the form of a colourless gum