Synthesis
General procedure for the synthesis of 1-Boc-3-cyano-4-pyrrolidinone from ethyl 2-(BOC-(2-cyanoethyl)amino)acetate: 2-(BOC-(2-cyanoethyl)amino)ethyl acetate (16.5 g), an oil, was dissolved in 50 mL of anhydrous ethanol. The solution was slowly added dropwise to 100 mL of anhydrous ethanol solution containing 4 g (0.17 mol) of sodium metal under heated reflux conditions and the reaction was continued at reflux for 1 hour. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure. The residue was dissolved in 100 mL of water and the aqueous layer was subsequently washed with ethyl acetate (30 mL x 2). The pH of the aqueous layer was adjusted to 4 with 1 mol/L hydrochloric acid and extracted with ethyl acetate. The organic phase was dried with anhydrous magnesium sulfate and filtered. The filtrate was concentrated to about 20 mL, filtered, and the filter cake was washed with a small amount of ethyl acetate and dried to give 16.5 g of white solid 1-Boc-3-cyano-4-pyrrolidinone in 68% yield.
References
[1] Archiv der Pharmazie, 2011, vol. 344, # 8, p. 523 - 529
[2] European Journal of Medicinal Chemistry, 2010, vol. 45, # 11, p. 5498 - 5506
[3] Patent: CN105585518, 2016, A. Location in patent: Paragraph 0024; 0026
[4] Journal of Medicinal Chemistry, 1997, vol. 40, # 22, p. 3584 - 3593
[5] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 24, p. 4399 - 4403
