反应详情

温度

70 °C

A mixture of 1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethanone (4.51 g, 20.58 mmol, Step-3), (R)-2-methylpropane-2-sulfinamide (3.74 g, 30.9 mmol) and tetraethyl orthotitanate (6.47 mL, 30.9 mmol) in tetrahydrofuran (23 mL) is stirred at 70° C. for 17 hours. The reaction mixture is cooled to 0° C., sodium borohydride (2.72 g, 72.0 mmol) is added there, and the mixture is stirred at same temperature for 1 hour. Saturated aqueous sodium hydrogen carbonate (50 mL) is added to the reaction mixture, and the mixture is stirred for 10 minutes. After filtration through a pad of celite (registered trademark), the filtrate is extracted with ethyl acetate (300 mL). The organic layer is washed with water (100 mL×2) and dried over sodium sulfate and concentrated in vacuo. The residue is purified by column chromatography on silica gel eluting with n-hexane/ethyl acetate (4:1 to 1:1) to give 6.25 g (94% yield) of the title compound as colorless oil.

1. temperatureThe reaction mixture is cooled to 0° C.
2. stirringthe mixture is stirred at same temperature for 1 hour
3. stirringthe mixture is stirred for 10 minutes
4. filtrationAfter filtration through a pad of celite (registered trademark)
5. extractionthe filtrate is extracted with ethyl acetate (300 mL)
6. washThe organic layer is washed with water (100 mL×2)
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated in vacuo
9. customThe residue is purified by column chromatography on silica gel eluting with n-hexane/ethyl acetate (4:1 to 1:1)