Benzyl 6-oxa-3-azabicyclo(3.1.0)hexane-3-carboxylate → (3S,4R)-benzyl 3-ethyl-4-hydroxypyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of benzyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate (4 g, 18.25 mmol) and Bromo(dimethylsulfide) copper(I) (3.75 g, 18.25 mmol) in Tetrahydrofuran (40 ml) was cooled to −30° C. A 3M solution of ethylmagnesium bromide (15.20 ml, 45.6 mmol) in Et2O was added dropwise to the reaction mixture over 35 minutes, maintaining an internal temperature of at or below −30° C. After the addition was complete, the resulting reaction mixture was allowed to warm to −15° C. over 45 minutes. At this time, the reaction was checked by HPLC. The reaction mixture was allowed to gradually warm up to rt and HPLC indicated that the reaction was complete. The reaction mixture was diluted with EtOAc (50 mL). The reaction mixture was then cooled in an ice bath and was quenched by slow addition of sat'd aq ammonium chloride (˜10 mL). The organic layer was separated and was washed with H2O (20 ml). The organic layer was concentrated and the crude was purified by silica gel chromatography to give (3S,4R)-benzyl 3-ethyl-4-hydroxypyrrolidine-1-carboxylate (17.25 g, 69.2 mmol, 69.0% yield). LCMS: (M+23)=242, t=1.87 min.

Provenance & Evidence