Hydrochloric Acid → 1-Azabicyclo(3.3.1)nonan-4-one

Participants

Reaction Steps

Anhydrous potassium t-butoxide (45.8 g) in anhydrous toluene (1.0 dm3) was heated at reflux and 1-carboethoxyethyl-3-carboethoxyethylpiperidine (35.0 g) in toluene (250 ml) was added over 2 hours. Reflux was maintained for a further 4 hours before cooling to room temperature and concentrated hydrochloric acid (300 ml) was added. The mixture was stirred for 1 hour, then the organic layer was separated and extracted with concentrated hydrochloric acid (225 ml×4). The combined acid extracts were heated at reflux for 16 hours, then basified to pH 10 with potassium carbonate and extracted with chlorofeny (300 ml×6). The combined organic extracts were dried (MgSO4) and concentrated in vacuo to an orange semi-solid (9.7 g). This was purified by chromatography (Alumina grade III) by gradient elution in 3-10% methanol in ethyl acetate. The title compound was isolated as light orange semi-solid (3.5 g). δH (360 MHz, CDCl3), 1.55 (1H, m, CHH), 1.7-1.8 (1H, m, CHH), 1.95 (2H, m, CH2), 2.4 (1H, s, CH), 2.55 (2H, m, CH2CO), 3.1-3.4 (6H, m, 3×CH2N); m/z 139 (M+) (100%).

Provenance & Evidence