(a) Synthesis of Intermediate 1a (5-bromo-3-formyl-4-methylpyridine): 3,5-dibromo-4-methylpyridine (3.8 g, 15.1 mmol) was dissolved in anhydrous tetrahydrofuran (150 mL) under argon protection and cooled to -100 °C (using a liquid nitrogen/ether bath). Slowly n-butyllithium (2.5 M hexane solution, 6.2 mL, 15.4 mmol) was added dropwise and the reaction mixture was stirred at -100 °C for 5 min. Subsequently, N,N-dimethylformamide (1.8 mL, 23.2 mmol) was added and stirring was continued at -100 °C for 20 min. The reaction mixture was then warmed to -78 °C and kept for 1 hour. Upon completion of the reaction, the reaction was quenched with saturated aqueous sodium bicarbonate and aqueous ammonium chloride and extracted with ether. The organic phases were combined, washed with saturated saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by silica gel column chromatography (eluent: 20% ethyl acetate/hexane) afforded Intermediate 1a (2.18 g, 72% yield) as a clear oil, which solidified slowly. The product was characterized by 1H NMR (300 MHz, CDCl3): δ 10.25 (s, 1H), 8.84 (s, 1H), 8.83 (s, 1H), 2.76 (s, 3H). Elemental analysis (C7H6BrNO) is consistent with theoretical values.
