4-Bromo-1-difluoromethoxy-2-fluoro-benzene

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 100 mL flask charged with DMF (23 mL) was added sodium 2-chloro-2,2-difluoroacetate (4.79 g, 31.4 mmol), potassium carbonate (2.60 g, 18.85 mmol), 4-bromo-2-fluorophenol (3 g, 15.71 mmol). Water (5.75 mL) was added and the reaction mixture was heated to 100° C. for 3 hours. Upon cooling to room temperature, the reaction mixture was diluted with Et2O (100 mL) and a 2 N NaOH solution (100 mL). The organic layer was removed and dried over anhydrous Na2SO4. Upon filtration the organic solution was concentrated on a rotary evaporator with the water bath at 4° C. to yield the title compound as a clear oil (1 g). NMR (400 MHz, CDCl3) δ 7.35 (dd, J=9.7, 2.3 Hz, 1H), 7.27 (ddd, J=8.7, 2.3, 1.5 Hz, 1H), 7.19-7.04 (m, 1H), 6.53 (t, J=73.0 Hz, 1H); ESIMS m/z 242 ([M+H]+). Upon cooling to room temperature The organic layer was removed dried over anhydrous Na2SO4 Upon filtration the organic solution was concentrated on a rotary evaporator with the water bath at 4° C.

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 100 mL flask charged with DMF (23 mL) was added sodium 2-chloro-2,2-difluoroacetate (4.79 g, 31.4 mmol), potassium carbonate (2.60 g, 18.85 mmol), 4-bromo-2-fluorophenol (3 g, 15.71 mmol). Water (5.75 mL) was added and the reaction mixture was heated to 100° C. for 3 hours. Upon cooling to room temperature, the reaction mixture was diluted with Et2O (100 mL) and a 2 N NaOH solution (100 mL). The organic layer was removed and dried over anhydrous Na2SO4. Upon filtration the organic solution was concentrated on a rotary evaporator with the water bath at 4° C. to yield the title compound as a clear oil (1 g). NMR (400 MHz, CDCl3) δ 7.35 (dd, J=9.7, 2.3 Hz, 1H), 7.27 (ddd, J=8.7, 2.3, 1.5 Hz, 1H), 7.19-7.04 (m, 1H), 6.53 (t, J=73.0 Hz, 1H); ESIMS m/z 242 ([M+H]+). Upon cooling to room temperature The organic layer was removed dried over anhydrous Na2SO4 Upon filtration the organic solution was concentrated on a rotary evaporator with the water bath at 4° C.