tert-Butanol → Benzyl 3-(tert-butoxycarbonylamino)-3-(fluoromethyl)pyrrolidine-1-carboxylate

Participants

Reaction Steps

To a solution of 1-(benzyloxycarbonyl)-3-(fluoromethyl)pyrrolidine-3-carboxylic acid (2.77 g, 9.85 mmol) in anhydrous t-BuOH (30 mL) was added triethylamine (6.86 mL, 49.24 mmol) and diphenyl phosphoryl azide (3.29 mL, 14.77 mmol). The mixture was heated at reflux for 16 hours under a nitrogen atmosphere. The mixture was cooled to ambient temperature, and partitioned between diethyl ether and water. The organic layer was separated and washed with saturated sodium bicarbonate solution and brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Biotage 40M, 20% ethyl acetate/hexanes) to afford benzyl 3-(tert-butoxycarbonylamino)-3-(fluoromethyl)pyrrolidine-1-carboxylate (2.27 g, 65%).

Provenance & Evidence