Sodium hydride → 4-(2,2-Difluoropropoxyl)pyrimidine-5-carbonitrile

To a suspension of sodium hydride (60% dispersed in mineral oil, 1.84 g, 46 mmol) in a THF (30.0 mL) was added 2,2-difluoropropan-1-ol (4.42 g, 46.0 mmol) at 0° C. The resulting mixture was stirred at room temperature for 1 hour, then 4-chloropyrimidine-5-carbonitrile (6 g, 43.2 mmol) was added in portions at 0° C. After addition, the reaction mixture was stirred at room temperature for 30 min. The reaction was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated to give the crude product, which was purified by silica gel column chromatography (10% ethyl acetate in petroleum ether) to afford the title compound (4.40 g, 22.1 mmol, 51% yield) as a yellow solid. MS (ESI) m/z 200.0 [M+H]+.

1. additionAfter addition
2. stirringthe reaction mixture was stirred at room temperature for 30 min
3. customThe reaction was quenched with saturated aqueous ammonium chloride solution
4. extractionextracted with ethyl acetate
5. dry with materialThe combined organic layers were dried over sodium sulfate
6. concentrationconcentrated
7. customto give the crude product, which
8. customwas purified by silica gel column chromatography (10% ethyl acetate in petroleum ether)

ORD record

ord-5fa32815113e4034b0be1ea5891a619b

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09156798B2