Over 5 min at -78 °C, 2-chloro-6-methoxypyridine (4.14 mL, 34.8 mmol) was slowly added dropwise to a mixture of tert-butyllithium (1.7 M pentane solution, 22.5 mL, 38.3 mmol) and 69 mL THF. The reaction mixture was stirred continuously at -78 °C for 1 h. Subsequently, N,N-dimethylformamide (3.5 mL, 45.0 mmol) was added and stirring was continued at -78 °C for 1.5 h. The reaction was completed with the addition of N,N-dimethylformamide (3.5 mL, 45.0 mmol). Upon completion of the reaction, the reaction was quenched by the addition of glacial acetic acid (4.0 mL, 69.0 mmol) and slowly warmed to room temperature over 30 minutes. Ether (200 mL) was added to dilute the reaction mixture, and the organic phase was washed sequentially with saturated aqueous sodium bicarbonate (50 mL) and brine (50 mL) and dried over anhydrous sodium sulfate. The organic phase was concentrated under reduced pressure and the crude product obtained was recrystallized from hexane to give 4.6 g (76% yield) of 2-chloro-6-methoxynicotinaldehyde as a light yellow solid, melting point: 67.0-68.0 °C. The product was analyzed by 1H NMR (1H NMR). The product was confirmed by 1H NMR (300 MHz, CDCl3): δ 10.29 (d, J = 0.8 Hz, 1H), 8.05 (d, J = 7.9 Hz, 1H), 7.02 (dd, J1 = 7.9 Hz, J2 = 0.8 Hz, 1H), 4.08 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 188.0, 164.2, 154.6, 140.0, 117.6, 117.5, 54.8; IR (ATR, cm-1): 3103, 2869, 1683, 1567, 1468, 1378, 1273, 1005.
