Ether (Et2O) was added to a 3L three-neck flask followed by 5-bromo-2-chloro-6-methylpyridine (56.97 g, 0.28 mol). The reaction mixture was cooled to -78 °C and n-butyllithium (n-BuLi, 132 mL, 0.33 mol) was slowly added dropwise through the addition funnel while ensuring that the reaction temperature was maintained below -70 °C. After the dropwise addition was completed, the mixture was continued to be stirred at -78 °C for 30 min. Subsequently, N,N-dimethylformamide (DMF, 43 mL, 0.56 mol) was added dropwise at the same temperature. After completion of the dropwise addition, the cooling bath was removed and the reaction mixture was allowed to gradually warm up to room temperature and stirred for 1.5 hours. Upon completion of the reaction, the reaction was quenched with brine (300 mL). The organic and aqueous layers were separated and the aqueous layer was extracted with ether (150 mL). The organic layers were combined and adjusted to pH 3-4 with dilute hydrochloric acid (HCl) in a conical flask, then washed with saturated aqueous sodium bicarbonate (NaHCO3) (300 mL). The organic layer was separated and concentrated to dryness. The crude product was recrystallized from a solvent mixture of ether/hexane (200 mL, 1:1) to give a light yellow crystalline solid (19 g). The filtrate was concentrated and further purified by column chromatography (eluent: ethyl acetate/hexane, 1:9) to give another batch of product (13 g). Combining the two batches of products, the total yield was 71%. The structure of the product was confirmed by 1H NMR (CDCl3): δ 2.87 (s, 3H), 7.35 (d, 1H, J=9.0 Hz), 8.07 (d, 1H, J=9.0 Hz), 10.31 (s, 1H).
