Trifluoroacetic anhydride → (2S,4R)-1-Boc-2-cyano-4-hydroxypyrrolidine

Temperature

-20 °C

(2S,4R)-tert-Butyl 2-carbamoyl-4-hydroxypyrrolidine-1-carboxylate 13c (74 g, 0.3217 mol) was dissolved in 740 mL of pyridine with stirring under argon atmosphere. The mixture was cooled to −20° C. followed by dropwise addition of trifluoroacetic anhydride (169 g, 0.804 mol). Upon completion of the addition, the reaction mixture was warmed up to room temperature. The reaction was monitored by TLC until the disappearance of the starting materials. The mixture was quenched with water and diluted with 0.8 L of ethyl acetate. The separated organic phase was washed with 500 mL of saturated brine and neutralized with 400 mL of concentrated hydrochloric acid to slight acidity. The resulting mixture was washed with 300 mL of aqueous sodium hydroxide solution (2 M) and 500 mL saturated brine successively, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain the title compound (2S,4R)-tert-butyl 2-cyano-4-hydroxypyrrolidine-1-carboxylate 13d (49.7 g, yield 73%) as a brown oil.

1. additionUpon completion of the addition
2. temperaturethe reaction mixture was warmed up to room temperature
3. customThe mixture was quenched with water
4. additiondiluted with 0.8 L of ethyl acetate
5. washThe separated organic phase was washed with 500 mL of saturated brine and neutralized with 400 mL of concentrated hydrochloric acid to slight acidity
6. washThe resulting mixture was washed with 300 mL of aqueous sodium hydroxide solution (2 M) and 500 mL saturated brine successively
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure

ORD record

ord-ef9938e2f815459ba3fdad055e2e5e68

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08415349B2