327-51-5

68-12-2

357405-75-5

Example 31 Preparation of 4-bromo-2,5-difluorobenzaldehyde To a solution of 2,5-dibromo-1,4-difluorobenzene (10.0 g, 36.77 mmol) in ether (150 mL) was added slowly and dropwise to butyllithium (2.5 M hexane solution, 14.86 mL, 37.15 mmol) at -78 °C under nitrogen protection. The reaction mixture was stirred at -78 °C for 30 min. Subsequently, a solution of anhydrous N,N-dimethylformamide (3.13 mL, 40.46 mmol) in ether (10 mL) was added dropwise and the reaction system was slowly warmed to room temperature over a period of 2 hours. Upon completion of the reaction, the reaction was quenched with saturated aqueous ammonium chloride solution (25 mL) and extracted with ether. The organic phases were combined, washed with saturated brine solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure (note: the product is highly volatile). The crude product was purified by fast column chromatography (silica gel as stationary phase, eluent 2-20% ethyl acetate in hexane solution) to afford the title compound 4-bromo-2,5-difluorobenzaldehyde as a light yellow solid (7.0 g, 86% yield). 1H NMR (400 MHz, CDCl3): δ 7.50 (dd, J = 5.08,8.92 Hz, 1H), 7.62 (dd, J = 5.80,7.68 Hz, 1H), 10.30 (d, J = 2.76 Hz, 1H).