N-Boc-4-oxo-L-proline

13726-69-7

84348-37-8

General procedure for the synthesis of (S)-1-(tert-butoxycarbonyl)-4-oxopyrrolidine-2-carboxylic acid from Boc-L-hydroxyproline: trichloroisocyanuric acid (75.6 g) was added to a solution (1000 mL) of ethyl acetate of (4R)-1-(tert-butoxycarbonyl)-4-hydroxy-L-proline (Formula IV, prepared according to the method of Example 1; 100 g). The reaction system was cooled to 0°C to -5°C. An ethyl acetate solution of TEMPO (3.38 g, dissolved in 50 mL of ethyl acetate) was slowly added at -5°C to 10°C and the reaction mixture was stirred at the same temperature for 20 minutes. Subsequently, the reaction system was warmed up to 25 °C to 30 °C and kept at this temperature and stirred for 60 min. Upon completion of the reaction, the reaction was quenched with deionized water (200 mL) and stirring was continued at 25°C to 30°C for 60 minutes. The reaction mixture was filtered through a Hyflo bed. The filtrate was washed with deionized water (2 x 200 mL) and partitioned. The organic layer was washed with aqueous sodium chloride (prepared from 40 g sodium hydroxide dissolved in 200 mL of deionized water). The organic layer was concentrated under reduced pressure at about 50°C to give a residue. The residue was dissolved in ethyl acetate (100 mL) and hexane (400 mL) was slowly added. The reaction mixture was stirred at 25 °C to 30 °C for 30 min and filtered, and the resulting solid was washed with a mixture of ethyl acetate (20 mL) and hexane (80 mL) and dried under reduced pressure at 40 °C to 45 °C to give 1-(tert-butoxycarbonyl)-4-oxo-L-proline. Yield: 95.9%.