108963-96-8

67-56-1

24424-99-5

98-79-3

108963-96-8

(1) Synthesis of (2S)-5-oxopyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (Compound 3): L-pyroglutamic acid (15.0 g) was suspended in methanol (60.0 mL), and thionyl chloride (27.6 g) was slowly added with stirring at a temperature lower than 30°C. The reaction was completed after 1 hour by HPLC. After 1 hr of reaction, HPLC monitoring showed completion of the reaction. The solvent was removed by distillation under reduced pressure and the residue was dissolved in ethyl acetate (200 mL). Triethylamine (13.5 g) was slowly added at a temperature below 30 °C, followed by filtration of the mixture. To the filtrate was added DMAP (1.5 g) in a single addition, followed by di-tert-butyl dicarbonate (Boc2O, 27.8 g) at a temperature below 30 °C. After HPLC monitoring showed the reaction to be complete, the mixture was cooled to 0 °C and 1N HCl (13.0 mL) was added and stirred at a temperature below 30 °C for 10 min. The organic layer was separated, washed with H2O (20.0 mL) and the solvent was evaporated under reduced pressure. To the resulting residue was added tert-butyl methyl ether (27.0 mL) and cooled to 0°C with stirring. The slowly precipitated crystals were filtered to give compound 3 (21.9 g, 77.3% yield).