Reaction #65226

Reaction equation

hydrazine

4-(Trifluoromethoxy)phenyl isocyanate

2-(3-methyl-5-isoxazolyl)-1-phenylethanone

N,N,N',N',-tetramethyldiaminomethane

trifluoroacetic acid

4,5-dihydro-4-(3-methyl-5-isoxazolyl)-3-phenyl-1H-pyrazole

→

title compound

4,5-Dihydro-4-(3-methyl-5-isoxazolyl)-3-phenyl-N-(4-trifluoromethoxyphenyl)-1H-pyrazole-1-carboxamide

Solvents

dichloromethane

acetic acid

dichloromethane

Conditions

Workup

1. 1
   Otherwas prepared
2. 2
   Temperaturewith cooling
3. 3
   workup.STIRRINGStirring
4. 4
   Temperatureto warm to ambient temperature
5. 5
   workup.STIRRINGstir for another 1.75 hr
6. 6
   Otherto react
7. 7
   workup.STIRRINGwith stirring for 2 hr
8. 8
   WashThe mixture was washed with saturated aqueous sodium bicarbonate solution
9. 9
   Dryingdried over sodium sulfate
10. 10
    Filtrationfiltered
11. 11
    workup.STIRRINGwith stirring
12. 12
    Otherto react for 1 hr
13. 13
    Otherto react for 5 min
14. 14
    WashIt was then washed with saturated aqueous sodium bicarbonate
15. 15
    Dryingdried over sodium sulfate
16. 16
    Filtrationfiltered
17. 17
    Concentrationconcentrated by evaporation under reduced pressure
18. 18
    ExtractionThe resulting solid was extracted with boiling ether and air
19. 19
    Otherdried

Procedure

A mixture of 20 mL of dichloromethane, 2.01 g (10 mmol) of 2-(3-methyl-5-isoxazolyl)-1-phenylethanone and 1.12 g (11 mmol) of N,N,N',N',-tetramethyldiaminomethane was prepared and cooled to -15° C. and 1.25 g (11 mmol) of trifluoroacetic acid in 5 mL of dichloromethane was added with cooling and stirring. Stirring was continued for 5 min at about 0° C. and then the mixture was allowed to warm to ambient temperature and stir for another 1.75 hr. A proton NMR spectrum of the mixture was taken which indicated complete disappearance of the starting material. Anhydrous hydrazine (0.96 g, 30 mmol) was added and the mixture was allowed to react with stirring for 2 hr. A proton NMR spectrum of the mixture indicated complete conversion to 4,5-dihydro-4-(3-methyl-5-isoxazolyl)-3-phenyl-1H-pyrazole. The mixture was washed with saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, and filtered. 4-(Trifluoromethoxy)phenyl isocyanate (2.19 g, 10.8 mmol) was then added with stirring. The mixture was allowed to react for 1 hr and then 1 mL of acetic acid was added and the mixture was allowed to react for 5 min. It was then washed with saturated aqueous sodium bicarbonate, dried over sodium sulfate, filtered, and concentrated by evaporation under reduced pressure. The resulting solid was extracted with boiling ether and air dried to obtain 3.1 g (72 percent of theory) of the title compound as a white solid melting at 195°-197° C.

Source