反应详情

温度

-15 °C

(2S,4R)-1-(tert-Butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid 13b (86.4 g, 0.374 mol) was dissolved in 1.2 L of tetrahydrofuran followed by addition of triethylamine (41 g, 0.411 mol) under argon atmosphere. The reaction mixture was cooled to −15° C., ethyl chlorformate (43.84 g, 0.411 mol) was added. After the mixture was stirred for 10 minutes, aqueous ammonia (236.8 mL) was added. The reaction mixture was slowly warmed up to 5° C. during 2 hours followed by addition of ammonium chloride (32 g). The reaction mixture was stirred for 30 minutes and separated. The separated organic phase was dried over anhydrous sodium sulfate, and the aqueous phase was extracted with ethyl acetate (100 mL×2). The combined organic extracts were concentrated under reduced pressure to obtain the title compound (2S,4R)-tert-butyl 2-carbamoyl-4-hydroxypyrrolidine-1-carboxylate 13c (74 g, yield 86%) as a white solid.

1. temperatureThe reaction mixture was slowly warmed up to 5° C. during 2 hours
2. stirringThe reaction mixture was stirred for 30 minutes
3. customseparated
4. dry with materialThe separated organic phase was dried over anhydrous sodium sulfate
5. extractionthe aqueous phase was extracted with ethyl acetate (100 mL×2)
6. concentrationThe combined organic extracts were concentrated under reduced pressure