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). After 1 hour, a further of NaH (178 mg) was added. The reaction was stirred at ambient temperature overnight then heated to reflux for 3 hours. The reaction was cooled to room temperature and chloromethyl chloroformate (0.60 mL, 6.69 mmol) was then added and the reaction stirred for 2 hours. The reaction was cooled to 0° C., diluted with ethyl acetate (20 mL) and quenched with aqueous saturated NaHCO3 solution (20 mL). 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 chloromethyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate (crude yield 1.54 g) as a 2:1 mixture of product/aripiprazole. The product was taken onto the next step crude.

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