反応 #342859

反応方程式

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

溶媒

N,N-dimethylformamide

benzene

acetic acid

dioxane

反応条件

後処理

1. 1
   workup.ADDITIONwas added
2. 2
   その他They were reacted at 70° C. for 1.5 hours
3. 3
   その他The resulting mixture was subjected to reaction at the same temperature for 1.5 hours
4. 4
   その他After completion of this reaction
5. 5
   ろ過the precipitated crystals were collected by filtration
6. 6
   洗浄washed with 10 ml of benzene
7. 7
   その他The crystals thus formed
8. 8
   その他they were reacted at 140° C. for 3 hours
9. 9
   その他After completion of the reaction
10. 10
    温度the reaction mixture was cooled to room temperature
11. 11
    その他the solvent was removed by distillation under reduced pressure
12. 12
    その他The residue was purified by a column chromatography (Wako Silica Gel C-200; eluent: chloroform)
13. 13
    その他to obtain an oily substance
14. 14
    その他they were reacted at 80° C. for 30 minutes
15. 15
    その他After completion of the reaction
16. 16
    温度the reaction mixture was cooled to room temperature
17. 17
    ろ過the precipitated crystals were collected by filtration
18. 18
    洗浄washed 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
    その他the resulting solution was subjected to reaction at room temperature for 30 minutes
21. 21
    ろ過the precipitated crystals were collected by filtration
22. 22
    洗浄washed 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
    その他After completion of the reaction
26. 26
    ろ過the resulting mixture was filtered
27. 27
    濃縮after which the filtrate was concentrated

実験手順

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.

出典