Methyl 2-(3-cyanopyridin-4-yl)acetate

5444-01-9

616-38-6

124870-33-3

Preparation of the intermediate 2-(3-cyanopyridin-4-yl)acetic acid methyl ester (I-65a): in a dry reaction flask, 4-methylnicotinonitrile (2.52 g, 21.33 mmol) was dissolved in anhydrous THF (15 mL) and cooled to -78 °C. A THF solution of 1 M LiHMDS (45 mL, 44.794 mmol) was slowly added under nitrogen protection, kept at -78 °C and stirred for 1 hour. Subsequently, dimethyl carbonate (1.98 mL, 23.464 mmol) was added dropwise to the reaction system and stirring was continued at -78 °C for 1 h. The temperature was then slowly raised to 0 °C and stirred for 2 h. The reaction was carried out by TLC. The progress of the reaction was monitored by TLC (unfolding agent: hexane solution of 30% ethyl acetate). Upon completion of the reaction, the reaction was quenched with saturated NH4Cl solution and then extracted with ethyl acetate. The organic layers were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography (eluent: hexane solution of 25% ethyl acetate) to give 530 mg of the target product in 14.10% yield. The product was characterized by 1H NMR (300 MHz, CDCl3): δ 8.9 (s, 1H), 8.79 (d, 1H), 7.4 (d, 1H), 3.9 (s, 2H), 3.79 (s, 3H).