Step 2: To a 20L three-necked round-bottomed flask was added deionized water (9L) and sodium hydroxide (900g, 22.50 mol, 3.07 eq.) in batches and stirred well. Under stirring, 1,3-diethyl 2-(6-chloropyrazin-2-yl)malonate (2 kg, 1.00 eq., crude) was added slowly and dropwise while the reaction temperature was controlled to be lower than 10°C. The reaction was carried out at a temperature below 10°C. The reaction was carried out at a temperature below 10°C. After completion of the reaction, the mixture was stirred at room temperature overnight and then cooled to 0°C. The pH of the reaction solution was adjusted to 9-10 with 37% hydrochloric acid and subsequently extracted with ethyl acetate (3 x 2 L). The organic phases were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was washed with petroleum ether (1 x 1.5 L) and methyl tert-butyl ether (1 x 1.5 L), dried again with anhydrous sodium sulfate and concentrated under reduced pressure to give 463.6 g (37% yield) of 2-(6-chloropyrazin-2-yl)acetic acid as a yellow solid.
