Reaction #1909813

Reaction equation

4-cyanomethyl-2-phenylthiazole

n-butyl lithium

hydrochloric acid

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

→

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

Yield 63.4%

Solvents

THF

THF

Conditions

Workup

1. 1
   Otherat −60° C.
2. 2
   workup.ADDITIONwas dropwise added
3. 3
   Otherat −60° C.
4. 4
   TemperatureThen, the resulting product was gradually heated
5. 5
   workup.STIRRINGstirred for 4 hours at room temperature
6. 6
   Extractionextracted with ethyl acetate
7. 7
   Washwashed with saturated saline
8. 8
   DryingThe resulting product was dried over sodium sulfate
9. 9
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
10. 10
    OtherThe residual product was purified through silica gel column chromatography
11. 11
    Otherto obtain the intended product from the fraction
12. 12
    Washeluted with chloroform
13. 13
    OtherThe resulting product was crystallized
14. 14
    Washwashed with diethyl ether

Procedure

0.72 g of 4-cyanomethyl-2-phenylthiazole was dissolved in 10 ml of dry THF, and 4.6 ml of n-butyl lithium (1.56 M hexane solution) was dropwise added thereto at −60° C. or lower in an argon atmosphere. After the resulting product was stirred at −60° C. or lower for 20 minutes, 0.84 g of 1-methyl-3,5-dichloropyrazole-4-carbonyl chloride as dissolved in 3 ml of dry THF was dropwise added thereto at −60° C. or lower. Then, the resulting product was gradually heated, and stirred for 4 hours at room temperature. The reaction mixture was poured into ice water, acidified with diluted hydrochloric acid, extracted with ethyl acetate, and washed with saturated saline. The resulting product was 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 the intended product from the fraction eluted with chloroform. The resulting product was crystallized and washed with diethyl ether to obtain 0.86 g of 3-(1-methyl-3,5-dichloropyrazol-4-yl)-2-(2-phenylthiazol-4-yl)-3-hydroxyacrylonitrile.

Source