Synthesis
In a three-necked flask equipped with a mechanical stirrer, condenser, and dropping funnel, methyl pyrazine-2-carboxylate (10 g, 72.4 mmol, 1 eq.) was dissolved dropwise over 35-40 min. into a stirred 90 mL solution of sodium methanolate (25% MeOH, 27.54 mL, 72.4 mmol, 1 eq.) in toluene in a 115 mL of ethyl formate solution. A yellow precipitate was formed. Stirring was continued at 110C for 3 hours. The reaction was cooled and the yellow precipitate was filtered and washed with a small amount of toluene. The solid was dissolved in 200 mL of saturated ammonium chloride and 400 mL of EtOAc. The aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over magnesium sulfate, filtered and evaporated to give ethyl 3-(2-pyrazinyl)-3-oxopropanoate. Yellow solid, yield 6.52 g, 50%.
