反应详情

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.

1. filtrationThe reaction was filtered
2. concentrationthe filtrate was concentrated
3. custompurified by silica gel column chromatography
4. washeluting with 30-40% ethyl acetate in hexanes