General procedure for the synthesis of 5-bromo-2-chloro-3-formylpyridine from 5-bromo-2-chloronicotinic acid methyl ester: To a stirring solution of 5-bromo-2-chloronicotinic acid methyl ester (10.0 g, 39.9 mmol) in dichloromethane (DCM, 100 mL) at -78 °C was slowly added dropwise diisobutylaluminum hydride (diBAL-H, 43.9 mL, 43.9 mmol (diBAL-H, 43.9 mL, 43.9 mmol, 1.6 M hexane solution). The reaction was kept at this temperature with continued stirring for 2 hours. Upon completion of the reaction, the reaction was quenched with 2M aqueous hydrochloric acid solution (50 mL) and stirred at room temperature for 30 minutes. Subsequently, the reaction mixture was filtered through diatomaceous earth to separate the organic and aqueous layers. The aqueous layer was extracted with ethyl acetate (2 x 100 mL). The organic layers were combined, washed with saturated saline (100 mL), dried over anhydrous sodium sulfate (Na2SO4) and filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by fast column chromatography (silica gel as stationary phase, 20-30% hexane solution of ethyl acetate as eluent) to give 6.50 g of 5-bromo-2-chloro-3-formaldehyde pyridine in 74% yield. The product was characterized by 1H NMR (400 MHz, DMSO-d6) and GCMS: 1H NMR δ 10.19 (s, 1H), 8.86 (brs, 1H), 8.40 (brs, 1H); GCMS m/z 218.94 (M).
