Uses
Boc-L-pyroglutamic acid benzyl ester is an intermediate in the synthesis of Avibactam, a novel non-beta-lactam β-lactamase inhibitor used in combination with ceftazidime for the treatment of complicated intra-abdominal infections, urinary tract infections, and pneumonia.
Synthesis
General procedure for the synthesis of benzyl (S)-2-(tert-butyl) 5-oxopyrrolidine-1,2-dicarboxylate from di-tert-butyl dicarbonate and benzyl (S)-5-oxopyrrolidine-2-carboxylate: Benzyl (S)-5-oxopyrrolidine-2-carboxylate (8 g, 36.5 mmol, 1 equiv.) was dissolved in dichloromethane (150 mL). The mixture was stirred and cooled to 0°C. 4-Dimethylaminopyridine (DMAP, 4.9 g, 40.1 mmol, 1.1 eq.) and di-tert-butyl dicarbonate ((Boc)2O, 8.75 g, 40.1 mmol, 1.1 eq.) were added sequentially. The reaction mixture was slowly warmed to room temperature and stirring was continued for 2 hours. Upon completion of the reaction, the reaction mixture was diluted with dichloromethane (250 mL) and washed sequentially with 1N aqueous hydrochloric acid (50 mL), saturated aqueous sodium bicarbonate (350 mL) and saturated aqueous sodium chloride. The organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography to afford the target product (S)-benzyl 2-tert-butyl 5-oxopyrrolidine-1,2-dicarboxylate (8.6 g, 73.8% yield). lc-MS (ESI+, m/z = 656, [2M + NH4]+).
References
[1] Tetrahedron Letters, 2002, vol. 43, # 19, p. 3499 - 3501
[2] Chemistry (Weinheim an der Bergstrasse, Germany), 2002, vol. 8, # 11, p. 2516 - 2525
[3] Journal of the Chemical Society - Perkin Transactions 1, 1996, # 6, p. 507 - 514
[4] Tetrahedron, 2004, vol. 60, # 45, p. 10277 - 10284
[5] Patent: US2014/248242, 2014, A1. Location in patent: Paragraph 0402; 0404
