Synthesis
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%.
References
[1] Patent: WO2015/19238, 2015, A1. Location in patent: Page/Page column 9
[2] Journal of the American Chemical Society, 2017, vol. 139, # 17, p. 6152 - 6159
[3] Organic Process Research and Development, 2015, vol. 19, # 1, p. 270 - 283
[4] Patent: WO2004/5249, 2004, A1. Location in patent: Page 30-31
[5] Tetrahedron Letters, 1993, vol. 34, # 46, p. 7489 - 7492
