Реакция #1605832

Уравнение реакции

isopropylchloroformate

Aripiprazole

diisopropylamine

n-BuLi

→

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

Растворители

2-methyltetrahydrofuran

Условия реакции

Обработка

1. 1
   workup.WAITAfter a further 10 minutes
2. 2
   workup.WAITThe reaction was held at −78° C. for 2 hours
3. 3
   Температураto warm to room temperature overnight
4. 4
   ДругоеThe reaction was quenched with saturated aqueous ammonium chloride solution (30 mL)
5. 5
   Экстракцияextracted with ethyl acetate (2×30 mL)
6. 6
   Промывкаwashed with saturated aqueous sodium hydrogen carbonate solution (30 mL), brine (30 mL)
7. 7
   Сушкаdried over MgSO4
8. 8
   Концентрированиеconcentrated
9. 9
   ДругоеThe crude product was purified by column chromatography on silica eluting with 1:1 ethyl acetate to dichloromethane to 2% methanol in 1:1 ethyl acetate to dichloromethane
10. 10
    Другоеto give the product
11. 11
    ДругоеThe product was recrystallized from isopropanol
12. 12
    Другоеto remove aliphatic impurities
13. 13
    Другоеwas purified by column chromatography
14. 14
    Промывкаeluting with 0 to 10% tetrahydrofuran in ethyl acetate
15. 15
    ДругоеThe product was triturated in heptane
16. 16
    Фильтрацияfiltered
17. 17
    Другоеto afford Compound-75 (0.593 g) as a colorless solid

Методика

To a solution of diisopropylamine (1.11 mL, 7.87 mmol) in 2-methyltetrahydrofuran (37 mL) at −5° C. was added n-BuLi (3.0 mL, 2.5 M in hexanes, 7.49 mmol) slowly. After 20 minutes, the reaction was cooled to −78° C. and Aripiprazole (1.68 g, 3.74 mmol) was added. After a further 10 minutes, isopropylchloroformate (9.37 mL, 1.0 mol in toluene, 9.37 mmol) was added. The reaction was held at −78° C. for 2 hours before allowing to warm to room temperature overnight. The reaction was quenched with saturated aqueous ammonium chloride solution (30 mL) and extracted with ethyl acetate (2×30 mL). The organics were combined, washed with saturated aqueous sodium hydrogen carbonate solution (30 mL), brine (30 mL), dried over MgSO4 and concentrated. The crude product was purified by column chromatography on silica eluting with 1:1 ethyl acetate to dichloromethane to 2% methanol in 1:1 ethyl acetate to dichloromethane to give the product. The product was recrystallized from isopropanol to remove aliphatic impurities. The product was not sufficiently pure so was purified by column chromatography eluting with 0 to 10% tetrahydrofuran in ethyl acetate. The product was triturated in heptane and filtered to afford Compound-75 (0.593 g) as a colorless solid.

Источник