General procedure for the synthesis of methyl 2-formylpyridine-4-carboxylate from methyl 2-(hydroxymethyl)isonicotinate: 2-(hydroxymethyl)isonicotinate (8.36 g, 50 mmol) was dissolved in dichloromethane (150 mL). Dess-Martin periodate (25 g, 58.94 mmol) was added and the reaction mixture was stirred at room temperature for 2 hours and 30 minutes. Sodium thiosulfate (59.3 g, 375.00 mmol) was dissolved in saturated sodium bicarbonate solution and subsequently added to the reaction mixture. The suspension was stirred vigorously at room temperature for 15 min, dichloromethane was added and the phases were separated. The aqueous phase was extracted twice with dichloromethane and the combined organic layers were dried over magnesium sulfate and concentrated. The residue was purified by automated rapid chromatography on a Biotage KP-SIL 340 g column using a 5-column volume gradient of heptane/ethyl acetate (80:20 to 65:35) as the mobile phase. Methyl 2-formylisonicotinate (7 g, 85% yield) was obtained as an off-white solid.1H NMR (400 MHz, CDCl3) δ 4.00 (s, 3H), 8.09 (dd, 1H), 8.49 (s, 1H), 8.95 (d, 1H), 10.15 (s, 1H). Mass spectrum m/z 165 (M)+.
