反应详情

Thionyl chloride (20 mL) was added to a mixture of 62.1 g (182 mmol) of 3-iodo-2-methyl-4-methylsulfonylbenzoic acid and 300 mL of 1,2-dichloroethane and the mixture was heated to reflux with stirring for 3 hours, absorbing the hydrogen chloride gas that evolved in an aqueous sodium hydroxide trap. The resulting solution was concentrated by evaporation under reduced pressure, diluted with 200 mL of toluene and reconcentrated by evaporation under reduced pressure. The resulting residue was dissolved in 100 mL of dichloromethane to obtain a first solution. A second solution was prepared by dissolving 22.3 g (270 mmol) of triethylamine and 24.7 g (270 mmol) of 1-ethyl-5-hydroxypyrazole in 200 mL of dichloromethane. This solution was cooled in an ice bath and the first solution was added to it dropwise with stirring and cooling. The resulting mixture was allowed to warm to ambient temperature and was then washed with cold 0.5N aqueous hydrochloric acid and then cold 5 percent aqueous potassium carbonate. It was then dried over magnesium sulfate and concentrated by evaporation under reduced pressure to obtain 84.2 g of a nearly colorless solid. This solid was slurried in 400 mL of dry acetonitrile and 1 mL (11 mmol) of acetone cyanohydrin and 37.7 g (270 mmol) of solid potassium carbonate were added. The mixture was allowed to stir overnight and was then concentrated by evaporation under reduced pressure. The residue was dissolved in water and the solution was extracted with ether and then acidified with 3N aqueous hydrochloric acid. The resulting mixture was extracted three times with dichloromethane and the combined extracts were dried over magnesium sulfate and concentrated by evaporation under reduced pressure. The gummy residue was crystallized by adding ethanol, heating to reflux, and allowing the solution to cool to obtain 63.3 9 (68 percent of theory) of the title compound as yellow crystals. The compound melts at 149-150° C.

1. temperaturethe mixture was heated
2. temperatureto reflux
3. customabsorbing the hydrogen chloride gas that
4. customevolved in an aqueous sodium hydroxide trap
5. concentrationThe resulting solution was concentrated by evaporation under reduced pressure
6. additiondiluted with 200 mL of toluene
7. customreconcentrated by evaporation under reduced pressure
8. dissolutionThe resulting residue was dissolved in 100 mL of dichloromethane
9. customto obtain a first solution
10. customA second solution was prepared
11. temperatureThis solution was cooled in an ice bath
12. additionthe first solution was added to it dropwise
13. stirringwith stirring
14. temperaturecooling
15. washwas then washed with cold 0.5N aqueous hydrochloric acid
16. dry with materialIt was then dried over magnesium sulfate
17. concentrationconcentrated by evaporation under reduced pressure
18. customto obtain 84.2 g of a nearly colorless solid
19. stirringto stir overnight
20. concentrationwas then concentrated by evaporation under reduced pressure
21. dissolutionThe residue was dissolved in water
22. extractionthe solution was extracted with ether
23. extractionThe resulting mixture was extracted three times with dichloromethane
24. dry with materialthe combined extracts were dried over magnesium sulfate
25. concentrationconcentrated by evaporation under reduced pressure
26. customThe gummy residue was crystallized
27. additionby adding ethanol
28. temperatureheating
29. temperatureto reflux
30. temperatureto cool