Synthesis
1-tert-butoxycarbonyl-3-pyrrolidone (120 g) and N,N-dimethylformamide (DMF, 600 mL) were added to a 1000 mL four-neck flask and the reaction system was cooled to 0-5°C and stirred. At this temperature, sodium hydride (26 g) was added in batches, followed by the slow dropwise addition of ethyl chloroformate (70.5 g) for a controlled dropwise time of about 40 minutes. After the dropwise addition was completed, the reaction was kept at 0-5°C and continued to be stirred for 2 hours. The progress of the reaction was monitored by thin layer chromatography (TLC) and after confirming the completion of the reaction, the reaction was quenched by slowly adding ice water (3 L). The pH of the reaction solution was adjusted to 7 with dilute hydrochloric acid and subsequently extracted with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford the intermediate 1-tert-butyl 3-ethyl 4-oxopyrrolidine-1,3-dicarboxylate in 85% yield.
