反应详情

To a suspension of aripiprazole (1 g, 2.23 mmol) in 2-methyltetrahydrofuran (20 mL) was added NaH (178 mg, 4.46 mmol). The reaction was heated to reflux for 1.5 hours then cooled to room temperature. Chloro(phenyl)methyl carbonochloridate (1.37 g, 6.69 mmol) was then added and the reaction stirred overnight at room temperature. The reaction was cooled to 0° C., diluted with ethyl acetate (20 mL) and quenched with aqueous saturated NaHCO3 (20 mL) solution. The reaction was extracted with ethyl acetate (3×20 mL) and the combined organics washed with brine (50 mL), then dried (MgSO4) and concentrated to give chloro(phenyl)methyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate (crude yield 2.10 g) as a 1:3 mixture of product/aripiprazole. The product was taken onto the next step crude.

1. temperatureThe reaction was heated
2. temperatureto reflux for 1.5 hours
3. temperatureThe reaction was cooled to 0° C.
4. customquenched with aqueous saturated NaHCO3 (20 mL) solution
5. extractionThe reaction was extracted with ethyl acetate (3×20 mL)
6. washthe combined organics washed with brine (50 mL)
7. dry with materialdried (MgSO4)
8. concentrationconcentrated