تفاعل #1605837

معادلة التفاعل

isobutyryl chloride

aripiprazole

diisopropylamine

n-BuLi

→

7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-1-isobutyryl-3,4-dihydroquinolin-2(1H)-one

المذيبات

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةwas re-cooled to 78° C.
2. 2
   درجة الحرارةAfter 2 h the reaction mixture was warmed to room temperature
3. 3
   workup.STIRRINGstirred for 1 h
4. 4
   أخرىA second reaction
5. 5
   غسيلThis mixture was washed with water
6. 6
   تجفيفdried over MgSO4
7. 7
   ترشيحfiltered
8. 8
   أخرىevaporated
9. 9
   workup.DISSOLUTIONThe residue was dissolved in diethyl ether
10. 10
    workup.ADDITION4M HCl in diethyl ether added
11. 11
    أخرىto form a precipitate
12. 12
    أخرىThe mother liquor was decanted
13. 13
    غسيلthe residual gum was washed with diethyl ether
14. 14
    أخرىThe gum was then partitioned between ethyl acetate and saturated sodium bicarbonate
15. 15
    أخرىthe organic layer separated
16. 16
    تجفيفAfter drying over MgSO4 and evaporation
17. 17
    أخرىthe residue was further purified on silica eluting with 1:1:0.1 dichloromethane/ethyl acetate/methanol
18. 18
    أخرىto give Compound-16 (1.3 g) as a yellow solid

الإجراء التجريبي

To a solution of diisopropylamine (1.3 mL, 8.9 mmol) in tetrahydrofuran (25 mL) at 78° C. was added n-BuLi (2.2M in hexanes, 4.1 mL, 8.9 mmol). The reaction mixture was warmed to 0° C. and after 10 min was re-cooled to 78° C. and aripiprazole (2.0 g, 4.5 mmol) added. The reaction mixture was stirred for 30 min and then isobutyryl chloride (0.7 mL, 6.7 mmol) added. After 2 h the reaction mixture was warmed to room temperature and stirred for 1 h. A second reaction was carried out under exactly the same conditions and the two reactions were combined. This mixture was washed with water, dried over MgSO4, filtered and evaporated. The residue was dissolved in diethyl ether and 4M HCl in diethyl ether added to form a precipitate. The mother liquor was decanted and the residual gum was washed with diethyl ether. The gum was then partitioned between ethyl acetate and saturated sodium bicarbonate, and the organic layer separated. After drying over MgSO4 and evaporation, the residue was further purified on silica eluting with 1:1:0.1 dichloromethane/ethyl acetate/methanol to give Compound-16 (1.3 g) as a yellow solid.

المصدر