1-Azabicyclo[3.2.1]octan-6-one → HCID 57548064, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of propargylaldehyde diethyl acetate (14.62 g, 114 mmol) and t-BuOK (14.92 g, 133 mmol) in 350 ml of anhydrous THF was stirred for 1 hour at −10° C. under N2. Then a suspension of 1-aza-bicyclo[3.2.1]octan-6-one (53, J. Med. Chem., 36, 1993, 683-689) (11.92 g, 95 mmol) in 100 ml of THF was added and the resulting homogeneous reaction mixture was stirred for another 2 hours at 0° C. Then the mixture was quenched with an aqueous acetic acid solution at 0° C. and concentrated in vacuo. Ethyl acetate was added and the organic layer was washed with 2 N NaOH, dried (Na2SO4), filtered and concentrated in vacuo. Purification by flash chromatography (dichloromethane/MeOH/NH4OH 93/7/0.5) afforded 6-(3,3-diethoxy-prop-1-ynyl)-1-azabicyclo[3.2.1]octan-6-ol (54) as an oil (20.87 g, 86%). LCMS (Method A): Rt: 1.18 min, ([M+H]+=254). 1H-NMR (400 MHz, CDCl3) δ 5.28 (s, 1H), 3.74-3.65 (m, 2H), 3.61-3.52 (m, 2H), 3.45 (d, J=13 Hz, 1H), 3.12-3.04 (m, 1H), 3.0-2.82 (m, 4H), 2.22-2.18 (m, 1H), 2.17-2.02 (m, 1H), 1.98-1.89 (m, 1H), 1.71-1.61 (m, 1H), 1.39-1.30 (m, 1H), 1.22 (t, J=7 Hz, 6H).

Provenance & Evidence