Synthesis
Step 2: Synthesis of benzyl 3-oxopiperazine-1-carboxylate
Sodium carbonate (24.77 g, 233.73 mmol, 3.00 eq.) and piperazin-2-one (7.80 g, 77.91 mmol, 1.00 eq.) were dissolved in a solvent mixture of ethyl acetate (70.00 mL) and water (70.00 mL) at 0 °C. Subsequently, benzyl chloroformate (16.79 g, 93.49 mmol, 13.99 mL, 95% purity, 1.20 eq.) was slowly added. The reaction mixture was stirred at 30 °C for 16 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was extracted with ethyl acetate (80 mL x 3). The organic layers were combined, washed with saturated aqueous sodium chloride (80 mL x 3), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. The crude product was purified by pulping (petroleum ether: ethyl acetate= 20:1,80mL) and filtered after stirring at 30°C for 15 min. The solid was dried under vacuum to obtain 4-Benzyloxycarbonyl-2-piperazinone (15.50 g, 66.17 mmol, 84.93% yield) as a white solid.
References
[1] Journal of Organic Chemistry, 1991, vol. 56, # 11, p. 3715 - 3719
[2] Tetrahedron, 2010, vol. 66, # 18, p. 3370 - 3377
[3] Patent: EP3269715, 2018, A1. Location in patent: Paragraph 0238; 0239
[4] European Journal of Medicinal Chemistry, 2017, vol. 132, p. 26 - 41
[5] European Journal of Medicinal Chemistry, 1981, vol. 16, # 3, p. 229 - 232
