Реакция #1605842

Уравнение реакции

dibenzyl phosphate

oxalyl chloride

dehydro-aripiprazole

potassium t-butoxide

→

7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)quinolin-2-yl diethyl phosphate

Растворители

dichloromethane

Условия реакции

Обработка

1. 1
   КонцентрированиеAfter 2 hours the reaction mixture was concentrated in vacuo
2. 2
   workup.DISSOLUTIONThe residue was dissolved in 2-methyltetrahydrfuran (5 mL)
3. 3
   Другоеwas quenched with water (25 mL) and 28% aq NH3 (15 mL)
4. 4
   workup.STIRRINGstirred for 10 minutes
5. 5
   ЭкстракцияThe reaction mixture was then extracted with ethyl acetate (2×40 mL)
6. 6
   ПромывкаThe combined organics were washed with water (50 mL) and brine (50 mL)
7. 7
   Сушкаthen dried (MgSO4)
8. 8
   Концентрированиеconcentrated in vacuo
9. 9
   ДругоеThe crude mixture was purified by column chromatography
10. 10
    Промывкаeluting with 5% methanol (1:1 ethyl acetate/dichloromethane)
11. 11
    Другоеto give the product
12. 12
    Другоеto remove these impurities

Методика

To a solution of dibenzyl phosphate (2.48 g, 8.91 mmol) in dichloromethane (25 ml) was added N,N-dimethyl formamide (1 drop) followed by oxalyl chloride (0.75 mL, 8.91 mmol). After 2 hours the reaction mixture was concentrated in vacuo. The residue was dissolved in 2-methyltetrahydrfuran (5 mL) and added to a suspension of dehydro-aripiprazole (1.66 g, 3.71 mmol) and potassium t-butoxide (0.92 g, 8.17 mmol) in 2-methyltetrahydrfuran (35 mL) at 0° C. under argon gas, then allowed to gradually warm to room temperature. After stirring overnight the reaction was quenched with water (25 mL) and 28% aq NH3 (15 mL) and stirred for 10 minutes. The reaction mixture was then extracted with ethyl acetate (2×40 mL). The combined organics were washed with water (50 mL) and brine (50 mL) then dried (MgSO4) and concentrated in vacuo. The crude mixture was purified by column chromatography eluting with 5% methanol (1:1 ethyl acetate/dichloromethane) to give the product. The 1H-NMR showed minor impurities still present (impurities not observed by LCMS). Various further purifications were attempted but failed to remove these impurities.

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