Phosphorus oxychloride → 4,5-Dichloro-6-(difluoromethyl)pyrimidine

100 ml of POCl3 was added dropwise to a solution of 65.0 g (0.36 mol) of 4-hydroxyl-5-chloro-6-(difluoromethyl)pyrimidin in 150 mL of toluene, the mixture was refluxed for 3-5 h after addition. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure to remove toluene and extra POCl3, and then poured into ice water. The water phase was extracted with ethyl acetate (3×50 ml), the organic phases were emerged, washed with saturated sodium bicarbonate, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was purified through silica column to give 64.5 g as yellow liquid, cooled to be solid in refrigerator with yield of 90%.

1. temperaturethe mixture was refluxed for 3-5 h
2. additionafter addition
3. concentrationthe reaction mixture was concentrated under reduced pressure
4. customto remove toluene and extra POCl3
5. additionpoured into ice water
6. extractionThe water phase was extracted with ethyl acetate (3×50 ml)
7. washwashed with saturated sodium bicarbonate
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified through silica column
12. customto give 64.5 g as yellow liquid
13. temperaturecooled

ORD record

ord-6c3d34aa1dd14b5bb6e81d04d5514877

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09447081B2