反应详情

To a solution of ethyl 3-amino-2,2-difluoropropanoate (401 g, 1.5 mol), cyclopentanone (140 mL, 1.575 mol) and sodium acetate (123 g, 1.5 mol) in THF (6.5 L) was added NaBH(OAc)3 (477 g, 2.25 mol) portionwise over a period of 40 min in ice bath. The resulting mixture was stirred vigorously at room temperature overnight. The mixture was added slowly to a stirring solution of ice (3300 mL), saturated aqueous sodium bicarbonate (3300 mL) and ethyl acetate (3300 mL) cooled in ice-salt bath over a period of 30 min. At this time the layers were separated and the pH of aqueous phase was further adjusted to 11 by addition of 25% aqueous NaOH while cooling in the bath. The aqueous phase was extracted with ethyl acetate (3.5 L×2) and all organic layers were combined, washed with cold saturated NaHCO3 (1.5 L×2), brine (1.5L), dried over MgSO4, filtered and concentrated to give 280 g of ethyl 3-(cyclopentylamino)-2,2-difluoropropanoate.

1. customAt this time the layers were separated
2. additionthe pH of aqueous phase was further adjusted to 11 by addition of 25% aqueous NaOH
3. temperaturewhile cooling in the bath
4. extractionThe aqueous phase was extracted with ethyl acetate (3.5 L×2)
5. washwashed with cold saturated NaHCO3 (1.5 L×2), brine (1.5L)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated