反应详情

To a mixture of (1,5-diphenyl-1H-pyrazol-4-yl)methanol (11.78 g), triethylamine (10 ml) and ethyl acetate (300 ml) was added dropwise methanesulfonyl chloride (4.5 ml) at 0° C. The mixture was stirred at room temperature for 1 hr. and the ethyl acetate layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give an oil. This oil was dissolved in N,N-dimethylformamide (100 ml) and the resulting solution was added dropwise to a solution of sodium diethyl malonate in N,N-dimethylformamide (prepared using diethyl malonate 20.33 g, sodium hydride (60% in oil, 4.88 g) and N,N-dimethylformamide 200 ml) at 0° C. The mixture was stirred at room temperature for 5 hrs., and poured into a 1N aqueous hydrochloric acid solution. The mixture was extracted with ethyl acetate. The ethyl acetate layer was washed successively with a 1N aqueous hydrochloric acid solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give an oil. A mixture of this oil, a 6N aqueous hydrochloric acid solution (100 ml) and acetic acid (50 ml) was heated under reflux for 5 hrs. The reaction mixture was cooled, concentrated and poured into water. The precipitated crystals were collected by filtration, washed with water, and dried to give 3-(1,5-diphenyl-1H-pyrazol-4-yl)propionic acid. yield: 68%. colorless needle crystals. melting point: 159-160° C. (recrystallized from acetone-hexane).

1. washand the ethyl acetate layer was washed successively with water and saturated brine
2. dry with materialdried over anhydrous magnesium sulfate
3. concentrationconcentrated
4. customto give an oil
5. stirringThe mixture was stirred at room temperature for 5 hrs
6. extractionThe mixture was extracted with ethyl acetate
7. washThe ethyl acetate layer was washed successively with a 1N aqueous hydrochloric acid solution and saturated brine
8. dry with materialdried over anhydrous magnesium sulfate
9. concentrationconcentrated
10. customto give an oil
11. additionA mixture of this oil
12. temperatureunder reflux for 5 hrs
13. temperatureThe reaction mixture was cooled
14. concentrationconcentrated
15. additionpoured into water
16. filtrationThe precipitated crystals were collected by filtration
17. washwashed with water
18. customdried