تفاعل #342859

معادلة التفاعل

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

المذيبات

N,N-dimethylformamide

benzene

acetic acid

dioxane

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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.

المصدر