Dibromodifluoromethane → 3-(Bromodifluoromethoxy)-2-nitropyridine

Temperature

20 °C

To a stirred solution of sodium hydride (856 mg, 21.41 mmol) in N-methylpyrrolidinone (20 mL) was added a solution of 2-nitropyridin-3-ol (2 g, 14.28 mmol) in N-methylpyrrolidinone (10 mL). The reaction mixture was stirred at 20° C. for 30 min followed by heating at 50° C. for another 30 min before cooling to 20° C. CF2Br2 (4.49 g, 21.41 mmol) was added dropwise and the resulting mixture was stirred at 20° C. for 18 h. Then CF2Br2 (8.99 g, 42.83 mmol) was added dropwise and the mixture was stirred at 20° C. for another 18 h. The reaction mixture was slowly quenched into saturated aqueous ammonium chloride solution (30 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with water (2×50 mL), brine (2×50 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography (silica gel, 100-200 mesh, 15% ethyl acetate in petroleum ether) affording product (890 mg, 23%): 1H NMR (400 MHz, chloroform-d) δ 8.53-8.51 (m, 1H), 7.99-7.97 (m, 1H), 7.72-7.69 (m, 1H).

1. temperatureby heating at 50° C. for another 30 min
2. temperaturebefore cooling to 20° C
3. stirringthe resulting mixture was stirred at 20° C. for 18 h
4. stirringthe mixture was stirred at 20° C. for another 18 h
5. customThe reaction mixture was slowly quenched into saturated aqueous ammonium chloride solution (30 mL)
6. extractionextracted with ethyl acetate (2×50 mL)
7. washThe combined organic layers were washed with water (2×50 mL), brine (2×50 mL)
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationconcentrated in vacuo
10. customThe resulting residue was purified by column chromatography (silica gel, 100-200 mesh, 15% ethyl acetate in petroleum ether)

ORD record

ord-1b7cc2696b624a14a9f729c8dcb2d95a

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365583B2