反应详情

To a mixture of 4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzene-1,2-diamine (552 mg), 2-ethylsulfanylbenzoic acid (401 mg), and pyridine (27 mL), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (422 mg) and 1-hydroxybenzotriazole (27 mg) were added at room temperature. The reaction mixture was stirred at room temperature for 5 hours, diluted with water, and extracted with ethyl acetate. The combined organic layer was dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was dissolved in a mixed solution of DMF (7.5 mL) and toluene (30 mL), and then p-toluenesulfonic acid (837 mg) was added at room temperature. The mixture was stirred with heating at 130° C. for 8 hours, and allowed to stand to cool to room temperature. Into the reaction mixture, saturated aqueous sodium hydrogen carbonate solution was poured, and extracted with ethyl acetate. The combined organic layer was dried over sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 97 mg of 2-(2-ethylsulfanyl-phenyl)-5-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-1H-benzimidazole (hereinafter, Present Compound 346).

1. additionwere added at room temperature
2. extractionextracted with ethyl acetate
3. dry with materialThe combined organic layer was dried over sodium sulfate
4. concentrationconcentrated under reduced pressure
5. dissolutionThe resulting residue was dissolved in a mixed solution of DMF (7.5 mL) and toluene (30 mL)
6. additionp-toluenesulfonic acid (837 mg) was added at room temperature
7. stirringThe mixture was stirred
8. temperaturewith heating at 130° C. for 8 hours
9. temperatureto cool to room temperature
10. additionInto the reaction mixture, saturated aqueous sodium hydrogen carbonate solution was poured
11. extractionextracted with ethyl acetate
12. dry with materialThe combined organic layer was dried over sodium sulfate
13. concentrationconcentrated under reduced pressure