反应详情

A solution of p-toluenesulfonylmethylisocyanide (12.3 g) in dimethoxyethane (60 ml) was added to a mixture of potassium t-butoxide (13.5 g) and dimethoxyethane (60 ml) at −78° C., and the resultant was stirred for 5 minutes. A solution of 1-benzyl-5-phenyl-1H-pyrazol-4-carbaldehyde (13.0 g) in dimethoxyethane (60 ml) was added to the mixture. After stirring at the same temperature for 1 hour, the mixture was stirred for 1 hour while raising the temperature. Methanol (180 ml) was added to the mixture, and refluxed for 1 hour. After cooling, the reaction solution was poured into saturated aqueous ammonium chloride solution, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated. The residue was subjected to silica gel column chromatography to obtain a colorless oily substance from the fraction eluted with ethyl acetate-hexane (1:2, volume ratio). A mixture of the resulting colorless oily substance, 4N aqueous sodium hydroxide solution (100 ml), tetrahydrofuran (100 ml) and ethanol (100 ml) was refluxed for 3 days. After cooling, the mixture was neutralized with dilute hydrochloric acid, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4) and concentrated. A mixture of the residue, ethyl iodide (6.5 ml), potassium carbonate (14.9 g) and N,N-dimethylformamide (150 ml) was stirred at room temperature for 3 hours. The reaction mixture was poured into water, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated. The residue was subjected to silica gel column chromatography to obtain a colorless oily substance from the fraction eluted with ethyl acetate-hexane (1:2, volume ratio). A mixture of the resulting oily substance, 5% palladium-carbon (30.0 g), formic acid (80 ml) and ethanol (160 ml) was refluxed for 1 hour. After cooling, the palladium-carbon was removed by filtration, and the filtrate was concentrated. The residue was dissolved in ethyl acetate, which was washed with saturated aqueous sodium bicarbonate solution, then with saturated aqueous sodium chloride solution, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography to obtain ethyl 3-phenyl-1H-pyrazol-4-ylacetate (4.65 g, yield 34%) as a colorless oily substance from the fraction eluted with ethyl acetate-hexane (1:1, volume ratio).

1. stirringAfter stirring at the same temperature for 1 hour
2. stirringthe mixture was stirred for 1 hour
3. temperaturewhile raising the temperature
4. temperaturerefluxed for 1 hour
5. temperatureAfter cooling
6. extractionwas extracted with ethyl acetate
7. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride solution
8. dry with materialdried (MgSO4)
9. concentrationconcentrated
10. customto obtain a colorless oily substance from the fraction
11. washeluted with ethyl acetate-hexane (1:2, volume ratio)
12. additionA mixture of the resulting colorless oily substance, 4N aqueous sodium hydroxide solution (100 ml), tetrahydrofuran (100 ml) and ethanol (100 ml)
13. temperaturewas refluxed for 3 days
14. temperatureAfter cooling
15. extractionwas extracted with ethyl acetate
16. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride solution
17. dry with materialdried (MgSO4)
18. concentrationconcentrated
19. additionA mixture of the residue, ethyl iodide (6.5 ml), potassium carbonate (14.9 g) and N,N-dimethylformamide (150 ml)
20. stirringwas stirred at room temperature for 3 hours
21. additionThe reaction mixture was poured into water, which
22. extractionwas extracted with ethyl acetate
23. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride solution
24. dry with materialdried (MgSO4)
25. concentrationconcentrated
26. customto obtain a colorless oily substance from the fraction
27. washeluted with ethyl acetate-hexane (1:2, volume ratio)
28. additionA mixture of the resulting oily substance, 5% palladium-carbon (30.0 g), formic acid (80 ml) and ethanol (160 ml)
29. temperaturewas refluxed for 1 hour
30. temperatureAfter cooling
31. customthe palladium-carbon was removed by filtration
32. concentrationthe filtrate was concentrated
33. dissolutionThe residue was dissolved in ethyl acetate
34. washwhich was washed with saturated aqueous sodium bicarbonate solution
35. dry with materialwith saturated aqueous sodium chloride solution, dried (MgSO4)
36. concentrationconcentrated