Thiobenzoic Acid → (2S,4S)-4-benzoylthio-2-(difluoromethyl)thiomethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

Participants

Reaction Steps

To a solution of (2S,4R)-2-(difluoromethyl)thiomethyl-4-hydroxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.01 g) and triphenylphosphine (1.1 g) in tetrahydrofuran (20 ml) was added dropwise a solution of diethyl azodicarboxylate (0.66 ml) in tetrahydrofuran (3 ml) at -10° C. to -5° C. with stirring. The mixture was stirred at the same temperature for 30 minutes. To the solution was added thiobenzoic S-acid (0.49 ml) at the same temperature and the mixture was stirred under ice-cooling for 2 hours. The reaction mixture was concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (60 ml). The solution was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride successively, dried over anhydrous magnesium sulfate, and evaporated in vacuo. The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of n-hexane and ethyl acetate (3:1, V/V). The fractions containing the desired compound were collected and evaporated in vacuo to give (2S,4S)-4-benzoylthio-2-(difluoromethyl)thiomethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.01 g).

Provenance & Evidence