Dimethylformamide → 4-Bromo-2,6-difluorobenzaldehyde

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Reaction Steps

n-BuLi (2.7M solution in heptane, 134 mL, 0.36 mol) was added drop wise at ˜75° C. to a solution of (i-Pr)2NH (51 ml, 0.36 mol) in THF (300 mL) and the mixture was stirred at the same temperature for 5 min. 1-Bromo-3,5-difluorobenzene (CAS 461-91-1) (70 g, 0.36 mol) in THF (100 ml) was added to the mixture at ˜80° C., and the mixture was stirred at the same temperature for 2 h. DMF (28 mL, 0.36 mol) was added to the mixture at ˜80° C., and the mixture was stirred at the same temperature for 15 min. A solution of AcOH in Et2O (1:1, 100 ml) was added to attain pH ˜4-5 at ˜80° C., and the reaction mixture was stirred at RT for 15 min. Water (500 mL) was added, and the layers were separated. The aqueous layer was extracted with Et2O (300 mL). The combined organic phases were washed with water, brine, dried with anhydrous Na2SO4 (100 g), evaporated and recrystallized from hexane to give the title compound (53.5 g, 67%, 0.24 mol) as white crystals. GC/MS data: 219 and 221 (M−H)+; 220 and 222 (M)+ (calculated for C7H3BrF2O 221). 1H NMR data (DMSO-d6): δ 10.15 (s, 1H, CHO), 7.71-7.65 (m, 2H, Ar—H).

Provenance & Evidence