Water → 1-Bromo-3-(difluoromethoxy)-5-fluorobenzene

Temperature

25 °C

To a solution of 3-bromo-5-fluorophenol (0.5 g, 2.6 mmol) in DMF (4.5 mL) was added K2CO3 (0.9 g, 6.54 mmol) and stirred at 25° C. for 10 min. Water (0.5 mL) was added to the above mixture followed by addition of 2-Chloro-2,2,-difluoroacetic acid sodium salt (0.6 g, 3.93 mmol) and stirring was continued at 100° C. for 3 h. The reaction mixture was cooled to 25° C. and diluted with ethyl acetate, washed with brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the crude, which was purified by column chromatography (using silica gel and 2% ethyl acetate in Hexane as eluent) to afford the desired compound (Int-45). 1H NMR (400 MHz, CDCl3) δ ppm 7.2-6.9 (2H, m), 6.8-6.7 (1H, d), 6.7-6.2 (1H, m).

1. stirringstirring
2. waitwas continued at 100° C. for 3 h
3. temperatureThe reaction mixture was cooled to 25° C.
4. washwashed with brine
5. dry with materialdried over anhydrous sodium sulphate
6. concentrationconcentrated under reduced pressure
7. customto afford the crude, which
8. customwas purified by column chromatography (using silica gel and 2% ethyl acetate in Hexane as eluent)

ORD record

ord-5800a0f975434b7d9fbbae5bc6d5d3e6

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09402833B2