532967-21-8

68-12-2

532967-21-8

General procedure for the synthesis of 2,6-difluoro-4-hydroxybenzaldehyde from N,N-dimethylformamide: At -78 °C, sec-butyllithium (1.3 M cyclohexane solution, 53 mL, 69.3 mmol) was slowly added to intermediates 19,1-(tert-butyldimethylsilyl)oxy-3,5-difluorobenzene (15.3 g, 62.6 mmol) and TMEDA (10.5 mL, 69.3 mmol) in a solution of tetrahydrofuran (200 mL) and stirred for 30 min at a maintained temperature of -78 °C. Subsequently, DMF (5.33 mL, 69.3 mmol) was added at the same temperature and stirring was continued for 1.5 hours. After the reaction was completed, 10% aqueous hydrochloric acid was added to adjust the pH to 4-5 (~200 mL) and then stirred at room temperature for 12 hours. The aqueous layer was extracted with ethyl acetate (200 mL) and the organic layer was separated. The organic layer was washed sequentially with saturated aqueous sodium bicarbonate, added sodium bicarbonate followed by water, and then adjusted the pH to 3-4 with hydrochloric acid, separated the organic layer, washed with brine, dried with anhydrous sodium sulfate, and finally evaporated in vacuum to obtain 2,6-difluoro-4-hydroxybenzaldehyde (9.7 g, 97% yield, 61.3 mmol) as a white solid.1H NMR (DMSO-d6) data: δ 11.54 (br.s, 1H, OH), 10.00 (s, 1H, CHO), 6.50-6.57 (m, 2H, Ar-H).