3-Oxabicyclo[3.1.0]hexane-6-carboxylicacid,ethylester(9CI)

1708-29-8

623-73-4

335599-07-0

The suspension was heated and stirred at 90-100 °C with 2,5-dihydrofuran (14 g, 200 mmol) and Cu(II)(acac)2 (1.05 g, 4 mmol). Subsequently, a benzene (PhH, 240 mL) solution of ethyl azidoacetate (27.3 g, 240 mmol) was slowly added dropwise to the reaction system over a period of 3 hours. After completion of the dropwise addition, the reaction mixture was cooled to room temperature and the solvent was removed by evaporation. The residue was dissolved in petroleum ether and purified by adsorption through a neutral alumina column (240 g of alumina per 10 mmol of diazoxide), eluting sequentially with 500 mL of petroleum ether and 500 mL of ether (Et2O). Removal of the solvent from the eluent gave the crude product ester, which was subjected to reduced pressure distillation at about 105°C (18-19 mmHg). The fractions were further purified by silica gel (SiO2) column chromatography using gradient elution with ethyl acetate (EtOAc)/hexane (0 to 30% EtOAc), resulting in 15.39 g (45.8% yield) of ethyl 3-oxo-bicyclo[3.1.0]hexane-6-carboxylate as the target product (Ref: I. Reichelt and H. J. Reissig , Chem. Ber. 1983, 116, 3895).