反应详情

n-Butyl lithium (2.5 M, 1.2 mL, 3.00 mmol) was added dropwise to a solution of diisopropylamine (0.406 mL, 3.0 mmol) in THF (5 mL) at 0° C. under nitrogen and stirred for 30 minutes. The mixture was then added to a solution of 3-oxo-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (0.675 g, 3.0 mmol) and 5-chloropyrimidine (0.343 g, 3.0 mmol) in THF (1.5 mL) and stirred at 0° C. for 1 hour. Water and ethyl acetate were added, the organics separated, dried over sodium sulphate, filtered and the solvent removed by evaporation under vacuum. The residue was purified by flash chromatography on silica eluting with 20-30% ethyl acetate/cyclohexane. The fractions containing the desired product were concentrated under vacuum to give the title compound (0.14 g). LCMS m/z 340.3 [M+H]+. R.T.=3.70 min (Analytical Method 3).

1. stirringstirred at 0° C. for 1 hour
2. dry with materialthe organics separated, dried over sodium sulphate
3. filtrationfiltered
4. customthe solvent removed by evaporation under vacuum
5. customThe residue was purified by flash chromatography on silica eluting with 20-30% ethyl acetate/cyclohexane
6. additionThe fractions containing the desired product
7. concentrationwere concentrated under vacuum