Реакция #1605836

Уравнение реакции

methylchloroformate

diisopropylamine

n-BuLi

aripiprazole

→

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

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
4. 4
   ДругоеAfter 2 hours the 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 10% methanol in 1:1 ethyl acetate to dichloromethane
10. 10
    Другоеto give the product
11. 11
    ДругоеThe product was triturated in heptane
12. 12
    Другоеto remove aliphatic impurities
13. 13
    Фильтрацияfiltered
14. 14
    Другоеto afford Compound-74 (0.824 g) as a colorless solid

Методика

To a solution of diisopropylamine (0.99 mL, 7.02 mmol) in 2-methyltetrahydrfuran (33 mL) at −5° C. was added n-BuLi (2.67 mL, 2.5 M in hexanes, 6.69 mmol) slowly. After 20 minutes, the reaction was cooled to −78° C. and aripiprazole (1.50 g, 3.34 mmol) was added. After a further 10 minutes, methylchloroformate (0.65 mL, 8.36 mmol) was added. The reaction was held at −78° C. for 2 hours before allowing to warm to room temperature. After 2 hours 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 10% methanol in 1:1 ethyl acetate to dichloromethane to give the product. The product was triturated in heptane to remove aliphatic impurities and then filtered to afford Compound-74 (0.824 g) as a colorless solid.

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