Реакция #1605831

Уравнение реакции

hexylchloroformate

Aripiprazole

diisopropylamine

n-BuLi

→

Hexyl 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 0 to 3% tetrahydrofuran in ethyl acetate
10. 10
    ДругоеThe product was triturated in heptane
11. 11
    Другоеto remove aliphatic impurities
12. 12
    Фильтрацияfiltered
13. 13
    Другоеdried
14. 14
    Другоеto afford Compound-59 (0.487 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, hexylchloroformate (1.53 mL, 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 0 to 3% tetrahydrofuran in ethyl acetate. The product was triturated in heptane to remove aliphatic impurities and then filtered and dried to afford Compound-59 (0.487 g) as a colorless solid.

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