Triethylamine → 4-chloro-6-(difluoromethyl)pyrimidine

6-(Difluoromethyl)-4(1H)-pyrimidinone (0.50 g, 3.42 mmol) was treated with triethylamine (0.477 mL, 3.42 mmol) and phosphorus oxychloride (1.595 mL, 17.11 mmol) and the resulting mixture was heated under reflux for 2 hours. The reaction mixture was allowed to cool to room temperature, evaporated under reduced pressure and the residue was poured into 2M aqueous hydrochloric acid solution (5 mL). This solution was extracted with DCM (×2). The DCM layers were combined, dried under magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography (Biotage SP4) eluting with a gradient of 0-20% ethyl acetate and iso-hexane. Product containing fractions were combined and evaporated under reduced pressure to give the title compound as a colourless oil (117 mg);

1. temperaturethe resulting mixture was heated
2. temperatureunder reflux for 2 hours
3. customevaporated under reduced pressure
4. additionthe residue was poured into 2M aqueous hydrochloric acid solution (5 mL)
5. extractionThis solution was extracted with DCM (×2)
6. customdried under magnesium sulfate
7. customevaporated under reduced pressure
8. customThe residue was purified by column chromatography (Biotage SP4)
9. washeluting with a gradient of 0-20% ethyl acetate and iso-hexane
10. additionProduct containing fractions
11. customevaporated under reduced pressure

ORDレコード

ord-bd2dd1497dcc4e258742735c05ecce37

出典データセット

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08796283B2