Reaction #1909817

Reaction equation

hydrochloric acid

4-tert-butylphenylacetonitrile

1-methyl-3,5-dichloropyrazole-4-carbonyl chloride

potassium t-butoxide

→

2-(4-tert-butylphenyl)-3-(1-methyl-3,5-dichloropyrazol-4-yl)-3-hydroxyacrylonitrile

Yield 31.7%

Solvents

THF

water

Conditions

Workup

1. 1
   Temperaturewith cooling with ice
2. 2
   Extractionextracted with ethyl acetate
3. 3
   WashThe organic layer was washed with water
4. 4
   Dryingdried with sodium sulfate
5. 5
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
6. 6
   workup.DISSOLUTIONThe residual product was dissolved in a mixed solvent of 10 ml of water and 10 ml of dioxane, and 0.38 g of potassium hydroxide
7. 7
   workup.ADDITIONwas added
8. 8
   Temperatureheated
9. 9
   Temperatureunder reflux for 4 hours
10. 10
    workup.WAITAfter having been left
11. 11
    Otherto be at room temperature
12. 12
    Extractionextracted with ethyl acetate
13. 13
    WashThe organic layer was washed with water
14. 14
    Dryingdried over sodium sulfate
15. 15
    workup.DISTILLATIONthe solvent was distilled off under reduced pressure
16. 16
    OtherThe residual product was purified through silica gel column chromatography

Procedure

1.00 g of 4-tert-butylphenylacetonitrile and 1.23 g of 1-methyl-3,5-dichloropyrazole-4-carbonyl chloride were dissolved in 20 ml of THF, and 1.01 g of potassium t-butoxide was added thereto with cooling with ice. After the resulting mixture was stirred overnight at room temperature, water was added thereto, acidified with diluted hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with water, and dried with sodium sulfate, and the solvent was distilled off under reduced pressure. The residual product was dissolved in a mixed solvent of 10 ml of water and 10 ml of dioxane, and 0.38 g of potassium hydroxide was added thereto and heated under reflux for 4 hours. After having been left to be at room temperature, this was acidified with diluted hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with water, and dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residual product was purified through silica gel column chromatography to obtain 0.64 g of 2-(4-tert-butylphenyl)-3-(1-methyl-3,5-dichloropyrazol-4-yl)-3-hydroxyacrylonitrile from the fraction eluted with n-hexane:ethyl acetate=2:1.

Source