反应详情

温度

0 °C

A solution of 39 g (388 mmol) of N,N-diisopropylamine in 500 ml of tetrahydrofuran is admixed at −5° C. with 232 ml (371 mmol) of a 1.6M solution of n-butyllithium in hexane. The solution is stirred for 30 minutes at 0° C. and then cooled to −78° C. 18.5 g (337 mmol) of n-propionitrile are then added dropwise. When addition is complete, the solution is stirred for 15 minutes. 30 g (169 mmol) of methyl pentafluoropropanoate are then slowly added. When addition is complete, the reaction mixture is stirred for a further 45 min at −78° C. The mixture is then heated to room temperature and stirred for one hour at room temperature. The reaction mixture is cooled to 0° C. and admixed with 700 ml of water. The pH of the solution is adjusted to 1 with conc. hydrochloric acid. The aqueous phase is extracted with ethyl acetate and the combined organic phases are dried over magnesium sulphate and concentrated by evaporation under reduced pressure on a rotary evaporator. The residue is dissolved in 200 ml of ethanol and admixed with 10.5 g (224 mmol) of methylhydrazine and 16 ml of conc. hydrochloric acid. The mixture is heated under reflux for five hours. The ethanol is removed under reduced pressure on a rotary evaporator and the pH of the aqueous phase is adjusted to 14. The aqueous phase is extracted several times with dichloromethane. The combined organic phases are dried over magnesium sulphate and concentrated by evaporation under reduced pressure on a rotary evaporator. This gives 13.0 g of 1,4-dimethyl-3-(pentafluoroethyl)-1H-pyrazole-5-amine (34%).

1. temperaturecooled to −78° C
2. additionWhen addition
3. stirringthe solution is stirred for 15 minutes
4. additionWhen addition
5. stirringthe reaction mixture is stirred for a further 45 min at −78° C
6. temperatureThe mixture is then heated to room temperature
7. stirringstirred for one hour at room temperature
8. temperatureThe reaction mixture is cooled to 0° C.
9. extractionThe aqueous phase is extracted with ethyl acetate
10. dry with materialthe combined organic phases are dried over magnesium sulphate
11. concentrationconcentrated by evaporation under reduced pressure on a rotary evaporator
12. dissolutionThe residue is dissolved in 200 ml of ethanol
13. temperatureThe mixture is heated
14. temperatureunder reflux for five hours
15. customThe ethanol is removed under reduced pressure on a rotary evaporator
16. extractionThe aqueous phase is extracted several times with dichloromethane
17. dry with materialThe combined organic phases are dried over magnesium sulphate
18. concentrationconcentrated by evaporation under reduced pressure on a rotary evaporator