21908-08-7

41438-38-4

21908-08-7

General procedure for the synthesis of ethyl 2-formylpyridine-4-carboxylate from ethyl 2,4-pyridinedicarboxylate: to an anhydrous solution of diethylpyridine-2,4-dicarboxylate (20.0 g, 89.6 mmol) in anhydrous tetrahydrofuran (300 mL) was added slowly and dropwise at -78 °C aluminum diisobutyl hydroxide (134.4 mL, 134.4 mmol, 1 mol/L in toluene). After the dropwise addition was completed, the reaction mixture was continued to be stirred at -78°C for 3 hours. Subsequently, the reaction solution was slowly poured into a pre-cooled mixture of acetic acid (50 mL) and water (250 mL) and gradually warmed to room temperature. After continued stirring for 1.5 h, the pH of the mixture was adjusted to 8 with sodium bicarbonate solution at 0 °C. Extraction was carried out with ethyl acetate (500 mL x 5), and the organic layers were combined and dried over anhydrous sodium sulfate and subsequently concentrated. Purification by silica gel column chromatography (petroleum ether: ethyl acetate = 40:1-10:1) afforded the target product ethyl 2-formylisonicotinate (13.0 g, 81% yield). lCMS m/z 180.