反应详情

To a solution of glacial acetic acid (80 mL) and concentrated hydrochloric acid (9 mL) was added 3,4-dihydro-4,4-dimethyl-1-(2H)-quinolinamine (9.5 g, 53.9 mmol) and 2-ketoglutaric acid (9.7 g, 65.1 mmol) and the suspension heated at reflux for 3 hours. After cooling the solvents were removed under reduced pressure and the residue dissolved in 500 mL of ethyl acetate. The ethyl acetate solution was washed with water (3×150 mL) and saturated aqueous sodium chloride (1×50 mL), dried over sodium sulfate,-filtered and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with 1-4% methanol in dichloromethane. Fractions containing product were combined and concentrated under reduced pressure to provide 4.45 g (34%) of the desired compound as a tan foam. An impure fraction was extracted with 1N sodium hydroxice (2×50 mL) and the combined aqueous layers washed with diethyl ether (20 mL) and made acidic with concentrated hydrochloric acid (8 mL). This aqueous mixture was extracted with dichloromethane (2×100 mL), followed by drying (Na2SO4) to provide an additional 2.55 g (19%) of desired product

1. temperaturethe suspension heated
2. temperatureat reflux for 3 hours
3. temperatureAfter cooling the solvents
4. customwere removed under reduced pressure
5. dissolutionthe residue dissolved in 500 mL of ethyl acetate
6. washThe ethyl acetate solution was washed with water (3×150 mL) and saturated aqueous sodium chloride (1×50 mL)
7. dry with materialdried over sodium sulfate
8. concentration-filtered and concentrated under reduced pressure
9. washeluting with 1-4% methanol in dichloromethane
10. additionFractions containing product
11. concentrationconcentrated under reduced pressure