1-Bromo-2-chloro-4-difluoromethoxybenzene synthesis

Yield:345226-22-4 56%

Reaction Conditions:

with tris[2-phenylpyridinato-C₂,N]iridium(III);caesium carbonate in N,N-dimethyl-formamide; for 0.75 h;Irradiation;Inert atmosphere;

Steps:

135 Example 135: Preparation of 1-bromo-2-chloro-4-(difluoromethoxy)benzene (C96)

4-Bromo-3-chlorophenol (2.00 g, 9.64 mmol), tris(2- phenylpyridine)iridium(III) (0.032 g, 0.048 mmol), potassium bromodifluoroacetate (4.11 g, 19.3 mmol), and cesium carbonate (9.42 g, 28.9 mmol) were combined in DMF (16.1 mL) in a round bottom flask under nitrogen. The reaction mixture was vigorously stirred and irradiated with a blue LED light. The reaction was nearly complete after 30 min but was stirred and irradiated for another 15 min. The reaction mixture was partitioned between Et20 and water. The organic phase was dried and concentrated onto silica gel. Purification by flash chromatography (0-10% EtOAc in hexanes gradient solvent system) provided the title compound as a clear oil (1.44 g, 56%): NMR (500 MHz, CDCl3) δ 7.60 (d, / = 8.8 Hz, 1H), 7.27 (d, / = 2.8 Hz, 1H), 6.94 (dd, / = 8.8, 2.6 Hz, 1H), 6.49 (t, / = 72.8 Hz, 1H); EIMS m/z 258.

References:

WO2019/84353,2019,A1 Location in patent:Paragraph 00286