反应详情

To a solution of 2-ethyl-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)-6-methylaniline (preparation as described in WO 08/074427) (106 mg, 0.3 mmol) in tetrahydrofuran (0.5 ml) was added pyridine (72.6 μl, 0.9 mmol) at 0 to 5° C. A solution of 2-bromo-3-nitrobenzoic acid chloride (87 mg, 0.33 mmol) in tetrahydrofuran (0.5 ml) was added. The reaction mixture was stirred at ambient temperature for 3 hours, then at reflux for 15 hours. After 15 hours, the reaction was not complete so N,N-dimethylacetamide (“DMA”) (0.1 equivalents) and more 2-bromo-3-nitrobenzoic acid chloride (0.2 equivalents) were added. The reaction mixture was stirred at ambient temperature for 41 hours. After 41 hours, the reaction was quenched by addition of saturated aqueous sodium hydrogen carbonate (10 ml) and the mixture extracted twice with ethyl acetate (2×20 ml). The combined organic extracts were dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 6:1) to give N-[2-ethyl-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)-6-methylphenyl]-2-bromo-3-nitrobenzamide (0.133 g, 76% yield).

1. temperatureat reflux for 15 hours
2. waitAfter 15 hours
3. additionwere added
4. stirringThe reaction mixture was stirred at ambient temperature for 41 hours
5. waitAfter 41 hours
6. customthe reaction was quenched by addition of saturated aqueous sodium hydrogen carbonate (10 ml)
7. extractionthe mixture extracted twice with ethyl acetate (2×20 ml)
8. dry with materialThe combined organic extracts were dried over sodium sulfate
9. concentrationconcentrated
10. customThe residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 6:1)