反应详情

50 g of pyrazole in 250 ml of abs. tetrahydrofuran is added dropwise in a nitrogen atmosphere within 1/2 hour at 20°-30°, with stirring and cooling, to 38.7 g of sodium hydride in 100 ml of abs. tetrahydrofuran. The reaction mixture is stirred for a further 3 hours at 40°; it is then cooled towards 5° and, with good cooling, 160.7 g of bromoacetic acid ethyl ester in 100 ml of abs. tetrahydrofuran is added dropwise at 0°-10° during 1 hour. Stirring is maintained overnight at room temperature; there is then added dropwise 150 ml of ethanol; stirring is continued for 1 hour, and the suspension is subsequently concentrated by evaporation. To the residue is added a solution of 74 g of NaOH tablets in 600 ml of 60% methanol (aqueous), and refluxing is carried out for 40 minutes. The solution is then cooled, and washed twice with 200 ml of ether. The aqueous phase is made acid to a congo-red indicator (about pH 2) with conc. hydrochloric acid at 5° with cooling, and the solution is continuously extracted during 24 hours with methylene chloride. The extract is concentrated by evaporation, and recrystallised from ether/tetrahydrofuran. The crystals melt at 167°-169°.

1. stirringThe reaction mixture is stirred for a further 3 hours at 40°
2. stirringStirring
3. stirringstirring
4. concentrationthe suspension is subsequently concentrated by evaporation
5. additionTo the residue is added a solution of 74 g of NaOH tablets in 600 ml of 60% methanol (aqueous)
6. temperaturerefluxing
7. waitis carried out for 40 minutes
8. temperatureThe solution is then cooled
9. washwashed twice with 200 ml of ether
10. customat 5°
11. temperaturewith cooling
12. extractionthe solution is continuously extracted during 24 hours with methylene chloride
13. concentrationThe extract is concentrated by evaporation
14. customrecrystallised from ether/tetrahydrofuran
15. custommelt at 167°-169°