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

To a suspension of sodium hydride (60% dispersed in mineral oil, 315 mg, 7.88 mmol) in THF (20 mL) was added 2,2-difluoropropan-1-ol (757 mg, 7.88 mmol) at 0° C. and the resulting mixture was stirred for 1 h. Then 4-chloropyrimidine-5-carbonitrile (1.00 g, 7.16 mmol) was added in portions and the mixture was stirred at room temperature for 30 min. The reaction was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate (500 mL×2). The combined organic layers were dried and concentrated and the residue was purified by silica gel chromatography column (12% ethyl acetate in petroleum ether) to afford the title compound (850 mg, 4.27 mmol, 58% yield) as a yellow solid. MS (ESI) m/z 200.0 [M+H]+.

1. stirringthe mixture was stirred at room temperature for 30 min
2. customThe reaction was quenched with saturated aqueous ammonium chloride solution
3. extractionextracted with ethyl acetate (500 mL×2)
4. customThe combined organic layers were dried
5. concentrationconcentrated
6. customthe residue was purified by silica gel chromatography column (12% ethyl acetate in petroleum ether)

ORD-Eintrag

ord-5f928f6d829f4273b51e7d716def00e3

Quelldatensatz

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09156798B2