L-Pyroglutamic Acid → tert-Butyl 5-oxo-L-prolinate

Participants

Reaction Steps

To a solution of L-pyroglutamic acid (100 g, 775 mmol) in tert-butyl acetate (1.3 L) was added 70% aqueous perchloric acid (25 mL). After stirring for 18 hours in a 3-liter round bottom flask sealed with a rubber septum, the reaction mixture was poured carefully into saturated aqueous sodium bicarbonate (800 mL) and extracted with ethyl acetate (1 L, then 300 mL). The combined organic layers were dried (sodium sulfate), filtered and concentrated to provide tert-Butyl L-pyroglutamate (100.5 g, 70% mass recovery). The tert-butyl L-pyroglutamate was dissolved in acetonitrile (1.5 L) with 4-dimethylaminopyridine (6.0 g, 49.1 mmol) and cooled to 0° C. A solution of di-tert-butyl-dicarbonate (154 g, 705 mmol) in acetonitrile (150 mL) was added over 30 min and after an additional 30 min the cooling bath was removed. After stirring at room temperature for 48 hours, the reaction mixture was concentrated. The residue was dissolved in ether (1 L) and hexanes (1 L), then washed with saturated aqueous sodium bicarbonate (2×100 mL) and saturated aqueous sodium chloride. The solution was dried (sodium sulfate), filtered and concentrated to give a yellow oil (140 g). The residue was purified by recrystallization from hexanes (800 ml) and ethyl acetate (25 mL), and the mother liquor was recrystallized from hexanes (300 mL) and ethyl acetate (10 mL) to give two crops of the title compound (122 g, 428 mmol, 55%) as a white solid. NMR data was consistent with previously reported material: R. A. August et al, J. Chem. Soc., Perkin Trans. 1 (1996) 507-514.

Provenance & Evidence