Methanol → HCID 68465097, compound

Participants

Reaction Steps

A mixture of 1-(3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]oct-7-yl)-2-bromo-1-ethanone (0.126 g, 0.360 mmol), silver trifluoromethanesulfonate (0.10 g, 0.39 mmol), and silver carbonate (0.10 g, 0.36 mmol) in methanol (4.0 mL) was stirred in the dark for 2 days at ambient temperature. The reaction was filtered, and the filtrate was concentrated and purified by silica gel column chromatography, eluting with 30-40% ethyl acetate in hexanes, to obtain 0.062 g (61% yield) of 1-(3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]oct-7-yl)-2-methoxy-1-ethanone as an oil. This was dissolved in dichloromethane (2.0 mL), treated with TFA (0.5 mL), and was stirred at ambient temperature for 2 h. The volatiles were evaporated, and the residue was vacuum dried to obtain 0.045 g of 1-(3-azabicyclo[3.3.0]oct-7-yl)-2-methoxy-1-ethanone trifluoroacetate, as an off-white solid (mixture of cis and trans isomers) (1H NMR (CD3OD, 300 MHz): δ 4.17 (s, 2H), 3.39 (s, 3H), 3.36-3.30 (m, 2H), 3.19-3.12 (m, 3H), 3.00-2.91 (m, 2H), 2.30-2.20 (m, 2H), 1.64-1.75 (m, 2H); MS (m/z): 184 (M+1)). This material exhibited Ki values at rat and human α4β2 of 32 nM and 31 nM respectively and did not pass HIS for α7.

Provenance & Evidence