反应详情

温度

-30 °C

A solution of borane-THF complex (188 mL, 1M solution in tetrahydrofuran), diluted with 200 mL tetrahydrofuran, was cooled to -30° C. under N2 atmosphere. A solution of 4-[(4-acetamidophenyl)methyl]-5-(trifluoromethyl)-3H-pyrazol-3-one (6 g, prepared as in Example 1 (except that 4-acetamidobenzylchloride was reacted with the β-keto ester anion in refluxing xylene) in tetrahydrofuran (300 mL) was added over 0.75 hours and the mixture allowed to warm gradually to ambient temperature with stirring for 15 hours. The reaction mixture was refluxed for 3 hours, then cooled in ice and quenched with aqueous sodium hydroxide solution (24 mL, 2.5N). The mixture was stirred for 2 hours at ice temperature and 15 hours at room temperature. Volatile materials were removed in vacuo on the rotary evaporator. The residue was solubilized in distilled water, brought to pH 7 with dilute, aqueous HCl solution and extracted with ethyl acetate. The extracts were washed with saturated brine solution, dried over MgSO4, filtered and concentrated. The residue was dissolved in isopropyl alcohol saturated with anhydrous HCl and cooled in ice. The precipitate was collected on a suction funnel and dried under vacuum (abderhalden apparatus) to afford the title compound as a pale yellow glass; sinters at 104° C., liquefies 169°-171° C.

1. additionwas added over 0.75 hours
2. temperatureto warm gradually to ambient temperature
3. temperatureThe reaction mixture was refluxed for 3 hours
4. temperaturecooled in ice
5. customquenched with aqueous sodium hydroxide solution (24 mL, 2.5N)
6. stirringThe mixture was stirred for 2 hours at ice temperature and 15 hours at room temperature
7. customVolatile materials were removed in vacuo on the rotary evaporator
8. additionwith dilute
9. extractionaqueous HCl solution and extracted with ethyl acetate
10. washThe extracts were washed with saturated brine solution
11. dry with materialdried over MgSO4
12. filtrationfiltered
13. concentrationconcentrated
14. dissolutionThe residue was dissolved in isopropyl alcohol saturated with anhydrous HCl
15. temperaturecooled in ice
16. customThe precipitate was collected on a suction funnel
17. customdried under vacuum (abderhalden apparatus)