Benzenesulfonyl chloride → (2S)-1-[2-(benzenesulfonyloxy)acetyl]-4,4-difluoropyrrolidine-2-carboxamide

Participants

Reaction Steps

(2S)-4,4-difluoro-1-(2-hydroxyacetyl)pyrrolidine-2-carbox amide (1.66 g) was suspended in acetonitrile (40 mL). To this suspension, N,N,N′,N′-tetramethyl-1,3-propanediamine (133 μL) and triethylamine (2.20 mL) were added. While the mixture was cooled in a salt-ice bath, benzenesulfonyl chloride (1.20 mL) was added dropwise. The reaction mixture was then stirred at the same temperature for 1 hour, followed by the addition of saturated brine (20 mL) and extraction with ethyl acetate (2×80 mL). The ethyl acetate extracts were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. To the resulting residue, a mixture of ethyl acetate and methanol (20:1, 30 mL) was added and the resulting crystal was collected by filtration to give (2S)-1-[2-(benzenesulfonyloxy)acetyl]-4,4-difluoropyrrolidine-2-carboxamide as a white crystal (1.60 g). The filtrate was concentrated under reduced pressure and the residue was purified on a silica gel column (ethyl acetate:methanol=20:1) to give additional (2S)-1-[2-(benzenesulfonyloxy)acetyl]-4,4-difluoropyrrolidine-2-carboxamide (0.58 g). The total amount of the product was 2.18 g (79% yield).

Provenance & Evidence