Ethyl D-(-)-pyroglutamate

64-17-5

4042-36-8

68766-96-1

General procedure for the synthesis of D-pyroglutamic acid ethyl ester from ethanol and D-(+)-pyroglutamic acid: thionyl chloride (10 ml, 139.68 mmol) was slowly added to an ethanolic solution (100 ml) of D-(+)-pyroglutamic acid (10 g, 69.84 mmol; purchased from Aldrich, Art. No. 422614) which was cooled down to -5 °C. The reaction mixture was stirred at room temperature for 3 hours. After completion of the reaction, the solvent was removed by vacuum evaporation and the residue was dissolved in ethyl acetate (350 ml). The organic phase was washed sequentially with water/triethylamine (40/12 ml) and water (40 ml). The organic phases were combined and concentrated by drying with anhydrous sodium sulfate. The concentrate was separated by column chromatography on a SNAP-Si column (50 g) with the eluent dichloromethane/ethyl acetate (gradient elution from 90/10 to 50/50). The fraction containing the target product was collected and the solvent was evaporated to give the first batch of ethyl D-pyroglutamate (D23) (6.4 g). The aqueous phase was saturated with sodium chloride and extracted with ethyl acetate (400 ml). The organic phase was washed with water (20 ml), dried over anhydrous sodium sulfate and concentrated to give the second batch of ethyl D-pyroglutamate (D23) (3.7 g). The product was characterized by 1H NMR (400 MHz, CDCl3), δ (ppm): 6.58 (broad single peak, 1H), 4.29-4.17 (multiple peaks, 3H), 2.53-2.29 (multiple peaks, 3H), 2.28-2.17 (multiple peaks, 1H), 1.35-1.22 (triple peaks, 3H).