反应详情

To a suspension of 4-cyanobenzoic acid (353 mg, 2.4 mmol) in dichloromethane (3 mL), was added oxalyl chloride (0.209 mL, 2.4 mmol). And then 10 micro-L of dimethylformamide was added to the mixture. The mixture was stirred for 1 hour and the solvent was removed under reduced pressure. The residue was azeotroped with dichloromethane. To the residue, was added 3 mL of dioxane. Then a solution of 2,2,2-trifluoro-N′-(4-methoxyphenyl)ethanehydrazonamide (466 mg, 2 mmol) and diisopropylethylamine (0.418 mL, 2.4 mmol) in 4.5 mL of dioxane was added to the mixture and the mixture was refluxed with stirring for 3.5 hours. The solvent was removed under reduced pressure, and dichloromethane and 0.1 N hydrochloric acid were added to the residue. The organic layer was separated, washed with 0.1 N hydrochloric acid, water, and brine, dried over magnesium sulfate. The crude product was purified by silica gel column chromatography (20:1-10:1 toluene-ethyl acetate). The desired product was rinsed with diisopropyl ether and dried in vacuo to give 4-[1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]benzonitrile (88 mg, 12.8% yield).

1. customthe solvent was removed under reduced pressure
2. customThe residue was azeotroped with dichloromethane
3. additionTo the residue, was added 3 mL of dioxane
4. temperaturethe mixture was refluxed
5. stirringwith stirring for 3.5 hours
6. customThe solvent was removed under reduced pressure, and dichloromethane and 0.1 N hydrochloric acid
7. additionwere added to the residue
8. customThe organic layer was separated
9. washwashed with 0.1 N hydrochloric acid, water, and brine
10. dry with materialdried over magnesium sulfate
11. customThe crude product was purified by silica gel column chromatography (20:1-10:1 toluene-ethyl acetate)
12. washThe desired product was rinsed with diisopropyl ether
13. customdried in vacuo