Reaktion #342859

Reaktionsgleichung

hydrochloric acid

4-hydroxy-2-methylaniline

2,3,5,6-tetrachloro-p-benzoquinone

methyl 7-(4-benzyloxycarbonyl-piperazin-1-yl)-3-oxo-4-heptenoate

→

1-(4-hydroxy-2-methylphenyl)-6-[2-(piperazine-1-yl)ethyl]-4-oxo-1,4-dihydronicotinic acid dihydrochloride

Lösungsmittel

N,N-dimethylformamide

benzene

acetic acid

dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added
2. 2
   SonstigeThey were reacted at 70° C. for 1.5 hours
3. 3
   SonstigeThe resulting mixture was subjected to reaction at the same temperature for 1.5 hours
4. 4
   SonstigeAfter completion of this reaction
5. 5
   Filtrationthe precipitated crystals were collected by filtration
6. 6
   Waschenwashed with 10 ml of benzene
7. 7
   SonstigeThe crystals thus formed
8. 8
   Sonstigethey were reacted at 140° C. for 3 hours
9. 9
   SonstigeAfter completion of the reaction
10. 10
    Temperaturthe reaction mixture was cooled to room temperature
11. 11
    Sonstigethe solvent was removed by distillation under reduced pressure
12. 12
    SonstigeThe residue was purified by a column chromatography (Wako Silica Gel C-200; eluent: chloroform)
13. 13
    Sonstigeto obtain an oily substance
14. 14
    Sonstigethey were reacted at 80° C. for 30 minutes
15. 15
    SonstigeAfter completion of the reaction
16. 16
    Temperaturthe reaction mixture was cooled to room temperature
17. 17
    Filtrationthe precipitated crystals were collected by filtration
18. 18
    Waschenwashed with 10 ml of dioxane
19. 19
    workup.DISSOLUTIONThe resulting crystals were dissolved in 10 ml of a 1N aqueous sodium hydroxide solution
20. 20
    Sonstigethe resulting solution was subjected to reaction at room temperature for 30 minutes
21. 21
    Filtrationthe precipitated crystals were collected by filtration
22. 22
    Waschenwashed with water
23. 23
    workup.DISSOLUTIONdissolved in 10 ml of dioxane
24. 24
    workup.ADDITIONFurther, 0.2 g of 5% by weight palladium carbon was added
25. 25
    SonstigeAfter completion of the reaction
26. 26
    Filtrationthe resulting mixture was filtered
27. 27
    Einengenafter which the filtrate was concentrated

Vorschrift

In 20 ml of benzene was dissolved 3.0 g of methyl 7-(4-benzyloxycarbonyl-piperazin-1-yl)-3-oxo-4-heptenoate, and 1.2 g of N,N-dimethylformamidodimethylacetal was added thereto. They were reacted at 70° C. for 1.5 hours. The reaction mixture was cooled to room temperature, and 1.0 g of 4-hydroxy-2-methylaniline was added thereto. The resulting mixture was subjected to reaction at the same temperature for 1.5 hours. After completion of this reaction, the precipitated crystals were collected by filtration, and washed with 10 ml of benzene. The crystals thus formed were dissolved in 20 ml of N,N-dimethylformamide, and they were reacted at 140° C. for 3 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, and the solvent was removed by distillation under reduced pressure. The residue was purified by a column chromatography (Wako Silica Gel C-200; eluent: chloroform) to obtain an oily substance. This oily substance was dissolved in 20 ml of dioxane, and 0.7 g of 2,3,5,6-tetrachloro-p-benzoquinone was added thereto, and they were reacted at 80° C. for 30 minutes. After completion of the reaction, the reaction mixture was cooled to room temperature, and the precipitated crystals were collected by filtration, and washed with 10 ml of dioxane. The resulting crystals were dissolved in 10 ml of a 1N aqueous sodium hydroxide solution, and the resulting solution was subjected to reaction at room temperature for 30 minutes. The reaction mixture was adjusted to a pH of 6.0 with acetic acid, and the precipitated crystals were collected by filtration, washed with water, and then dissolved in 10 ml of dioxane and 5 ml of water. Further, 0.2 g of 5% by weight palladium carbon was added thereto. The resulting mixture was subjected to hydrogenation under atmospheric pressure for 2 hours. After completion of the reaction, to the reaction mixture was added 5 ml of 2N hydrochloric acid, and the resulting mixture was filtered, after which the filtrate was concentrated to obtain 0.4 g of 1-(4-hydroxy-2-methylphenyl)-6-[2-(piperazine-1-yl)ethyl]-4-oxo-1,4-dihydronicotinic acid dihydrochloride having a melting point of 140°-148° C.

Quelle