反应详情

To 1,3,4,5-tetrahydro-4-(methoxyphenyl)-3-(2-propenyl)-6-(trifluoromethyl)-2H-1-benzazepin-2-one (3.40 g; 9.05 mmole), potassium bicarbonate (1.81 g; 18.1 mmole), and potassium iodide (catalytic amount) suspended in methylethyl ketone (55 ml) was added a 2.15M solution of 2-dimethylaminoethyl chloride (5.1 ml; 10.9 mmole) in toluene, with stirring. After refluxing for ~30 minutes, an additional 5.1 ml of the amine was added, and an additional 1.81 g of potassium bicarbonate was added after 1.5 hours of reflux. After six hours of reflux, the mixture was rotary evaporated and the residue was dissolved into ethyl acetate, and washed with water. The organic layer was dried (magnesium sulfate) and concentrated leaving 4.07 g of viscous, oily free amine of the title compound. This material was flash chromatographed (silica gel/0.5-3% gradient methanol:dichloromethane) and the cis containing fractions were combined and concentrated, dissolved in ether, washed with 1N sodium bicarbonate, dried (magnesium sulfate), and acidified with hydrogen chloride saturated ether. The mixture was concentrated and the white solid triturated in ether. The solid product was collected by suction-filtration, yielding 1.39 g of the title compound; melting point 226°-228° C.

1. temperatureAfter refluxing for ~30 minutes
2. temperatureof reflux
3. temperatureAfter six hours of reflux
4. customthe mixture was rotary evaporated
5. dissolutionthe residue was dissolved into ethyl acetate
6. washwashed with water
7. dry with materialThe organic layer was dried (magnesium sulfate)
8. concentrationconcentrated