Ethyl Acetate → Bicyclo[3.2.1]octan-8-one

Participants

Reaction Steps

3-Bromo-2-bromomethyl-propionic acid ethyl ester (5.48 g, 20 mmol) was added to a mixture of 1-cyclopent-1-enyl-pyrrolidine (2.74 g, 20 mmol) and Hünig's base (3.5 mL) in MeCN (15 mL) with vigorous stirring. An exothermic reaction ensued, bringing the mixture to reflux. The mixture was refluxed for 16 h, cooled, and poured into 100 mL of EtOAc with stirring. The resulting solid (3.33 g) was collected by filtration, dissolved in 0.5 M aqueous HCl (100 mL) and stirred with EtOAc (100 mL) for 48 h. The organic layer was separated and concentrated to give 8-oxo-bicyclo[3.2.1]octane-endo-3-carboxylic acid ethyl ester (1.0 g, 5.1 mmol) as a colourless oil. This was dissolved in EtOH (50 mL),treated with a solution of hydroxylamine hydrochloride (1.04 g, 15 mmol) and sodium acetate trihydrate (2.04 g, 15 mmol) in water (10 mL) and heated at reflux for 16 h. The solution was cooled, concentrated, diluted with water (100 mL) and extracted with DCM. The DCM extracts were dried (MgSO4), concentrated and purified by flash chromatography (20→30% EtOAc/hexane) to give the oxime (270 mg) as a colourless oil. 1H NMR (CDCl3, 360 MHz) δ 9.85 (1 H, bs, N—OH), 4.20 (2 H, q, J=7.1 Hz, CH2—O), 3.36 (1 H, bs, bridgehead H), 2.63-2.56 (4 H, m), 2.15-2.04 (2 H, m), 1.76-1.69 (4 H, m), 1.30 (3 H, t, J=7.1 Hz, —Me). m/z 212 (M+H)+.

Provenance & Evidence