تفاعل #1605832

معادلة التفاعل

isopropylchloroformate

Aripiprazole

diisopropylamine

n-BuLi

→

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

المذيبات

2-methyltetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   workup.WAITAfter a further 10 minutes
2. 2
   workup.WAITThe reaction was held at −78° C. for 2 hours
3. 3
   درجة الحرارةto warm to room temperature overnight
4. 4
   أخرىThe reaction was quenched with saturated aqueous ammonium chloride solution (30 mL)
5. 5
   استخلاصextracted with ethyl acetate (2×30 mL)
6. 6
   غسيلwashed with saturated aqueous sodium hydrogen carbonate solution (30 mL), brine (30 mL)
7. 7
   تجفيفdried over MgSO4
8. 8
   تركيزconcentrated
9. 9
   أخرىThe 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
    أخرىto give the product
11. 11
    أخرىThe product was recrystallized from isopropanol
12. 12
    أخرىto remove aliphatic impurities
13. 13
    أخرىwas purified by column chromatography
14. 14
    غسيلeluting with 0 to 10% tetrahydrofuran in ethyl acetate
15. 15
    أخرىThe product was triturated in heptane
16. 16
    ترشيحfiltered
17. 17
    أخرىto afford Compound-75 (0.593 g) as a colorless solid

الإجراء التجريبي

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.

المصدر