General procedure for the synthesis of 1-bromo-2-(difluoromethoxy)-4-fluorobenzene from sodium difluorochloroacetate and 2-bromo-5-fluorophenol:
1. to a solution of 2-bromo-5-fluorophenol (3 g, 15.7 mmol) in DMF (5 ml) was added cesium carbonate (7.7 g, 23.56 mmol, 1.5 eq.) and sodium difluorochloroacetate (6 g, 39.26 mmol, 2.5 eq.).
2. The reaction mixture was heated and stirred at 100 °C for 15 hours.
3. After completion of the reaction, the reaction was terminated with water and ethyl acetate (3 x 50 ml).
4. The organic layer was separated, washed with water and brine, and then dried over anhydrous sodium sulfate.
5. The solvent was removed by pressurized distillation to obtain the crude product.
6. The crude product was purified by column chromatography (silica gel 60-120, eluent: 10% hexane solution of ethyl acetate) in 58% (2.2 g) yield.
