The general procedure for the synthesis of methyl 5-cyano-3-pyridinecarboxylate from methyl 5-bromonicotinate and cuprous cyanide was as follows: methyl 5-bromonicotinate (2.16 g, 10.0 mmol, 1.0 eq.) and cuprous(I) cyanide (1.79 g, 20.0 mmol, 2.0 eq.) were dissolved in anhydrous DMF (10 mL), and the reaction was carried out at reflux for 15 hours. Upon completion of the reaction, it was cooled to room temperature and the reaction mixture was filtered through a diatomaceous earth pad and rinsed with ethyl acetate (100 mL). Formation of a black precipitate was observed in the filtrate. Subsequently, the filtrate was washed with saturated saline (3 x 100 mL). The organic layer was dried with anhydrous sodium sulfate and concentrated by rotary evaporation at 40 °C to give 546 mg (33.7% yield) of light yellow solid product. The crude product was further purified by silica gel column chromatography (column size: 80 mm in diameter × 20 mm in height) with an eluent of 20-35% ethyl acetate/hexane mixture, resulting in 501 mg (30.9% yield) of methyl 5-cyano-3-pyridinecarboxylate as an off-white solid. Mass spectrometry result: m/e 163.07 ([M+H]+).
