Phosphorus oxychloride → 4-Chloro-2-(3-chlorophenyl)-6-(trifluoromethyl)pyrimidine

Temperature

100 °C

A 250-mL round bottom flask was charged with 2-(3-chlorophenyl)-6-(trifluoromethyl)pyrimidin-4(3H)-one (3.60 g, 13.1 mmol). POCl3 (14.4 mL, 157 mmol) was cautiously added at 0° C. The resulting mixture was stirred at 100° C. for 3.5 h. After cooling to room temperature, the mixture was concentrated under reduced pressure. The residue was dissolved in dichloromethane (50 mL) and treated with aqueous sodium, bicarbonate until the pH˜8. The aqueous layer was extracted with dichloromethane (4×25 mL). The combined organic extract was washed the saturated sodium chloride (20 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica chromatography using hexanes/dichloromethane (3:1) as eluent to afford the title compound (3.36 g, 87%) as a white solid. MW=293.07. 1H NMR (CDCl3, 500 MHz) δ 8.49 (t, J=1.5 Hz, 1H), 8.39 (dt, J=8.0, 1.5 Hz, 1H), 7.57 (s, 1H), 7.53 (ddd, J=8.0, 2.0, 1.0 Hz, 1H), 7.45 (t, J=8.0 Hz, 1H).

1. temperatureAfter cooling to room temperature
2. concentrationthe mixture was concentrated under reduced pressure
3. dissolutionThe residue was dissolved in dichloromethane (50 mL)
4. additiontreated with aqueous sodium, bicarbonate until the pH˜8
5. extractionThe aqueous layer was extracted with dichloromethane (4×25 mL)
6. extractionThe combined organic extract
7. washwas washed the saturated sodium chloride (20 mL)
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by silica chromatography

ORD record

ord-6505a042c46f46fda41afb3fe9bb7396

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09221843B2