反应详情

To a suspension of sodium hydride (360 mg; 7.5 mmole; 50% oil dispersion/prewashed with dry ether several times) in dry dimethylformamide (30 ml), cooled at 0°-5° C. was added a solution of 1,3,4,5-tetrahydro-3-(methoxycarbonyl)-4-(methoxyphenyl)-7-(trifluoromethyl)-2H-1-benzazepin-2-one (1.9 g; 5 mmole) in dry dimethylformamide (15 ml) dropwise and with stirring. The mixture was stirred for an additional 20 minutes at 0°-5° C., whereupon bromomethylmethyl ether (800 μl; 10 mmole) was added dropwise, and stirring was continued at this temperature for an additional hour. Excess sodium hydride was destroyed by the addition of water, and the mixture was diluted with ether and washed with water. The aqueous layer was extracted with ether (three times) and the combined extracts were dried (magnesium sulfate) and concentrated. The crude oily residue was flash chromatographed (silica gel/5-25% ethyl acetate:hexane) to obtain 1.67 g of the title compound as an oil.

1. temperaturecooled at 0°-5° C.
2. additionwas added dropwise
3. stirringstirring
4. waitwas continued at this temperature for an additional hour
5. customExcess sodium hydride was destroyed by the addition of water
6. additionthe mixture was diluted with ether
7. washwashed with water
8. extractionThe aqueous layer was extracted with ether (three times)
9. dry with materialthe combined extracts were dried (magnesium sulfate)
10. concentrationconcentrated
11. customchromatographed (silica gel/5-25% ethyl acetate:hexane)