Reacción #1605838

Ecuación de reacción

aripiprazole

pivaloyl chloride

→

title compound

7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2-yl pivalate

Disolventes

pyridine

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturato warm to room temperature
2. 2
   TemperaturaAfter a further 5 minutes the temperature was increased to 50° C. for approximately 19 hours
3. 3
   Temperaturato cool to room temperature
4. 4
   OtroThe two reaction mixtures
5. 5
   Otroquenched with approximately methanol (5 mL)
6. 6
   OtroThe majority of the pyridine was removed in vacuo
7. 7
   Otrothe residue partitioned between dichloromethane (30 mL) and saturated NaHCO3 solution (30 mL)
8. 8
   ExtracciónThe aqueous phase was extracted with dichloromethane (2×30 mL)
9. 9
   Lavadothe combined organic extracts washed with brine (20 mL)
10. 10
    Secadodried over MgSO4
11. 11
    FiltraciónAfter filtration
12. 12
    Otrothe volatiles were removed (toluene and methanol/dichloromethane azeotrope)
13. 13
    Otrothe residue purified by silica chromatography
14. 14
    Lavadoeluting first with dichloromethane

Procedimiento

To a stirred solution of aripiprazole (0.1 g, 0.223 mmol) in pyridine (1 mL) at 0° C. was added pivaloyl chloride (0.055 mL, 0.446 mmol). After stirring at 0° C. for 5 minutes the reaction was allowed to warm to room temperature. After a further 5 minutes the temperature was increased to 50° C. for approximately 19 hours. The reaction was allowed to cool to room temperature. The reaction was repeated in a similar manner using of aripiprazole (1.75 g, 3.90 mmol). The two reaction mixtures were combined and quenched with approximately methanol (5 mL). The majority of the pyridine was removed in vacuo and the residue partitioned between dichloromethane (30 mL) and saturated NaHCO3 solution (30 mL). The aqueous phase was extracted with dichloromethane (2×30 mL) and the combined organic extracts washed with brine (20 mL) and dried over MgSO4. After filtration, the volatiles were removed (toluene and methanol/dichloromethane azeotrope) and the residue purified by silica chromatography eluting first with dichloromethane followed by ethyl acetate/dichloromethane/methanol (1:1:0.04) to give the title compound (1.19 g, 54%).

Fuente