Reacción #1605845

Ecuación de reacción

aripiprazole

NaH

Chloromethyl chloroformate

→

chloromethyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate

Disolventes

2-methyltetrahydrofuran

2-methyltetrahydrofuran

ethyl acetate

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGthe reaction stirred for 2 days
2. 2
   Otroquenched with aqueous saturated NaHCO3 solution (50 mL)
3. 3
   ExtracciónThe reaction was extracted with ethyl acetate (3×50 mL)
4. 4
   Lavadothe combined organics washed with brine (100 mL)
5. 5
   Secadodried (MgSO4)
6. 6
   Concentraciónconcentrated

Procedimiento

To a suspension of aripiprazole (2 g, 4.46 mmol) in 2-methyltetrahydrofuran (40 mL) was added NaH (357 mg, 8.92 mmol). After 20 minutes, further 2-methyltetrahydrofuran (20 mL) was added to aid stirring. Chloromethyl chloroformate (1.19 mL, 13.38 mmol) was then added and the reaction stirred for 2 days. The reactions were combined for work up. The reaction was cooled to 0° C., diluted with ethyl acetate (50 mL) and quenched with aqueous saturated NaHCO3 solution (50 mL). The reaction was extracted with ethyl acetate (3×50 mL) and the combined organics washed with brine (100 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 2.59 g) as 3:2 mixture of product/aripiprazole. The product was not purified due to instability during silica chromatography and so taken onto the next step crude.

Fuente