Under nitrogen protection, 2-oxopiperidine-4-carboxylic acid (250 g, 1.74 mol) was dissolved in methanol (2.5 L), and N,N'-dicyclohexylcarbodiimide (DCC, 540 g, 2.62 mol) was added under stirring at room temperature, and the reaction was continued to be stirred for 16 hours. The progress of the reaction was monitored by thin layer chromatography (TLC) and after confirming the complete consumption of raw materials, the reaction mixture was diluted with ether (2.5 L) and stirring was continued for 2 hours. The resulting solid by-product (N,N'-dicyclohexylurea, DCU) was removed by filtration, and the filtrate was concentrated under reduced pressure to afford a solid containing the target product methyl 2-oxopiperidine-4-carboxylate mixed with a small amount of DCU and other impurities. The resulting solid was ground again with ether (2 L) and then treated with a solvent mixture of methanol and ethyl acetate (1:9, 3 L) for 3 hours. The undissolved DCU was removed by filtration and the filtrate was evaporated to afford the target compound methyl 2-oxopiperidine-4-carboxylate (100 g, 36% yield) as an off-white solid. The product was confirmed by 1H NMR (400 MHz, DMSO-d6) and LCMS (m/z: 158.2 [M+H]+) characterization.
