Triethylamine → (2S,4S)-4-fluoro-1-[2-(tert-butyldimethylsilyloxy)acetyl]pyrrolidine-2-carbonitrile

(2S,4S)-4-fluoro-1-[2-(tert-butyldimethylsilyloxy)acetyl]pyrrolidine-2-carboxamide (6.05 g) was dissolved in dehydrated tetrahydrofuran (130 mL). While the solution was cooled in an ice bath, triethylamine (9.70 mL) was added, followed by dropwise addition of trifluoroacetic anhydride (4.30 mL) and subsequent stirring at room temperature for 1 hour. The reaction mixture was then concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate (400 mL). The ethyl acetate solution was washed successively with water (50 mL), saturated aqueous sodium bicarbonate solution (50 mL) and saturated brine (50 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified on a silica gel column (hexane:ethyl acetate=1:2) to give (2S,4S)-4-fluoro-1-[2-(tert-butyldimethylsilyloxy)acetyl]pyrro lidine-2-carbonitrile as a white solid (5.63 g).

1. temperatureWhile the solution was cooled in an ice bath
2. concentrationThe reaction mixture was then concentrated under reduced pressure
3. dissolutionthe resulting residue was dissolved in ethyl acetate (400 mL)
4. washThe ethyl acetate solution was washed successively with water (50 mL), saturated aqueous sodium bicarbonate solution (50 mL) and saturated brine (50 mL)
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customThe resulting residue was purified on a silica gel column (hexane:ethyl acetate=1:2)

ORD record

ord-320033dc6faf4f0b969ad8ad326e12da

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07915427B2