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

(2S,4S)-4-fluoro-1-(2-hydroxyacetyl)pyrrolidine-2-carboxa mide (4.10 g) and imidazole (3.27 g) were dissolved in dehydrated N,N-dimethylformamide (100 mL). While the solution was cooled in an ice bath, a solution of tert-butyldimethylsilyl chloride (3.62 g) in dehydrated N,N-dimethylformamide (30 mL) was added dropwise and the mixture was stirred at room temperature for 1 hour. The reaction mixture was then concentrated under reduced pressure and dissolved in ethyl acetate (300 mL). The ethyl acetate solution was washed successively with water (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 (eluant=ethyl acetate:methanol=10:1) to give (2S,4S)-4-fluoro-1-[2-(tert-butyldimethylsilyloxy)acetyl]pyrro lidine-2-carboxamide as a white solid (6.17 g).

1. temperatureWhile the solution was cooled in an ice bath
2. concentrationThe reaction mixture was then concentrated under reduced pressure
3. dissolutiondissolved in ethyl acetate (300 mL)
4. washThe ethyl acetate solution was washed successively with water (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 (eluant=ethyl acetate:methanol=10:1)

ORD record

ord-187e3863c1cd4be6bc566030adf93c85

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07915427B2