Lithium Hexamethyldisilazide → (R)-2-(2-ethoxy-5-oxo-2,5-dihydrofuran-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-amino-5-ethoxy-5H-furan-2-one (0.08 g, 0.58 mmol) in tetrahydrofuran (10 mL) at −78° C. under nitrogen was dropwise added a solution of 1M lithium bis(trimethylsilyl)amide in tetrahydrofuran (0.64 mL, 0.64 mmol). The reaction was stirred 3 h at 0° C. A solution of 2-fluorocarbonyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.20 g, 0.77 mmol) in tetrahydrofuran (3 mL) was added dropwise. The reaction was stirred for 16 h at room temperature. The mixture was diluted with ethyl acetate, was washed with 10% sodium bisulfate, saturated sodium bicarbonate, and brine, was dried over sodium sulfate, and was evaporated. Purification by flash chromatography (SiO2) eluted with 35:65 ethyl acetate:hexanes afforded (R )-2-(2-ethoxy-5-oxo-2,5-dihydrofuran-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.05 g, 26% yield). Also isolated was starting 4-amino-5-ethoxy-5H-furan-2-one (0.03 g, 36% yield).

Provenance & Evidence