반응 #4200

반응 방정식

4-methyl-N-[5-bromo-2-(1,2,3,4-tetrahydro-1-quinolinyl)phenyl]piperazinecarboxamide

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수율 56.0%

10-Bromo-7-(4-methyl-1-piperazinyl)- 2,3-dihydro-1H-quino[1,8-ab][1,5]benzodiazepine

수율 56.0%

용매

phosphorus oxychloride

반응 조건

후처리

1. 1
   온도under reflux under nitrogen for 6 hours
2. 2
   기타excess phosphorus oxychloride was removed at aspirator pressure
3. 3
   온도with heating
4. 4
   온도The residue was chilled in an ice-bath (with exclusion of moisture)
5. 5
   workup.ADDITIONtreated with ice-cold 2N sodium hydroxide solution (250 ml) and dichloromethane (250 ml)
6. 6
   기타triturated until the residue
7. 7
   workup.DISSOLUTIONdissolved
8. 8
   기타The organic phase was separated
9. 9
   세척washed again with 2N sodium hydroxide solution, twice with water
10. 10
    건조dried over sodium sulfate
11. 11
    농축concentrated in vacuo
12. 12
    여과filtered
13. 13
    workup.STIRRINGthe filrate was stirred 15 minutes with charcoal
14. 14
    여과After filtration
15. 15
    workup.STIRRINGthe solution was stirred with dichloromethane (100 ml)
16. 16
    workup.ADDITIONby the addition of cold 2N sodium hydroxide solution
17. 17
    기타The organic phase was separated
18. 18
    세척washed twice with water
19. 19
    건조dried over sodium sulfate
20. 20
    여과After filtration
21. 21
    농축the solution was concentrated

실험 절차

A stirred solution of 4-methyl-N-[5-bromo-2-(1,2,3,4-tetrahydro-1-quinolinyl)phenyl]piperazinecarboxamide (8.6 g, 0.020 mole) in phosphorus oxychloride (200 ml) was heated under reflux under nitrogen for 6 hours. The reaction mixture was cooled to room temperature and excess phosphorus oxychloride was removed at aspirator pressure with heating. The residue was chilled in an ice-bath (with exclusion of moisture), and treated with ice-cold 2N sodium hydroxide solution (250 ml) and dichloromethane (250 ml). The mixture was stirred and triturated until the residue dissolved. The organic phase was separated, washed again with 2N sodium hydroxide solution, twice with water, dried over sodium sulfate, and concentrated in vacuo. The residue was taken up in 4N hydrochloric acid (100 ml), filtered, and the filrate was stirred 15 minutes with charcoal. After filtration, the solution was stirred with dichloromethane (100 ml), and the mixture was made alkaline by the addition of cold 2N sodium hydroxide solution. The organic phase was separated, washed twice with water, dried over sodium sulfate, and boiled 15 minutes with charcoal. After filtration, the solution was concentrated to give 4.6 g (56%) of product, as an oil, which crystallized on standing. The product was taken up in boiling methanol (20 ml) and allowed to crystallize first at room temperature, then in the refrigerator. Recrystallization from methanol afforded the analytical sample, mp 153°-156° C.

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