3-Bromo-4-difluoromethoxybenzaldehyde synthesis

Yield:1155878-02-6 74%

Reaction Conditions:

with caesium carbonate in N,N-dimethyl-formamide at 75; for 18 h;

Steps:

REAGENT R-1.1.3-bromo-4-(difluoromethoxy)benzaldehyde

[0537] To a mixture of 3-bromo-4-hydroxybenzaldehyde (5.0 g, 24.88 mmol) and cesium carbonate (20.3 g, 62.20 mmol) in N,N-dimethylformamide (75 mL) was sodium chlorodifluoroacetate (7.6 g, 49.76 mmol) was added and the reaction mixture was stirred at 75 oC for 18 hours. It was partitioned with ethyl acetate (250 mL) and water (100 mL), the organic phase was washed with water (2x 100 mL), 1M aqueous hydrochloric acid (2x 150 mL) and brine (150 mL), dried over anhydrous sodium sulfate and concentrated. The resulting crude was purified by gradient silica gel flash chromatography (0-25% ethyl acetate in hexanes) to give 3-bromo-4-(difluoromethoxy) benzaldehyde (R-1.1.) (4.6 g, 74%). 1H-NMR (300 MHz, d6-DMSO): 9.90 (s, 1H), 8.22 (d, 1H), 8.04 (dd, 1H), 7.56 (d, 1H), 7.44 (t, 1H). MS (EI) for C8H5BrF2O2: 234 [M+H].

References:

WO2017/223516,2017,A1 Location in patent:Paragraph 0537