Реакция #1605838

Уравнение реакции

aripiprazole

pivaloyl chloride

→

title compound

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

Растворители

pyridine

Условия реакции

Обработка

1. 1
   Температураto warm to room temperature
2. 2
   ТемператураAfter a further 5 minutes the temperature was increased to 50° C. for approximately 19 hours
3. 3
   Температураto cool to room temperature
4. 4
   ДругоеThe two reaction mixtures
5. 5
   Другоеquenched with approximately methanol (5 mL)
6. 6
   ДругоеThe majority of the pyridine was removed in vacuo
7. 7
   Другоеthe residue partitioned between dichloromethane (30 mL) and saturated NaHCO3 solution (30 mL)
8. 8
   ЭкстракцияThe aqueous phase was extracted with dichloromethane (2×30 mL)
9. 9
   Промывкаthe combined organic extracts washed with brine (20 mL)
10. 10
    Сушкаdried over MgSO4
11. 11
    ФильтрацияAfter filtration
12. 12
    Другоеthe volatiles were removed (toluene and methanol/dichloromethane azeotrope)
13. 13
    Другоеthe residue purified by silica chromatography
14. 14
    Промывкаeluting first with dichloromethane

Методика

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%).

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