Reaction #1563944

Reaction equation

2-Chloro-2,2,-difluoroacetic acid sodium salt

Water

3-bromo-5-fluorophenol

K2CO3

→

desired compound

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

Solvents

ethyl acetate

DMF

Conditions

Workup

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued at 100° C. for 3 h
3. 3
   TemperatureThe reaction mixture was cooled to 25° C.
4. 4
   Washwashed with brine
5. 5
   Dryingdried over anhydrous sodium sulphate
6. 6
   Concentrationconcentrated under reduced pressure
7. 7
   Otherto afford the crude, which
8. 8
   Otherwas purified by column chromatography (using silica gel and 2% ethyl acetate in Hexane as eluent)

Procedure

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).

Source