反应详情

To a suspension of 2-fluoro-3-nitrobenzoic acid (6.3 g, 34 mmol) in dichloromethane (20 ml) was added oxalyl chloride (4.3 ml) at ambient temperature, followed by N,N-dimethylformamide (0.2 ml). The reaction mixture was stirred for 1 hour at ambient temperature and then heated to reflux for 3 hours. The reaction mixture was allowed to cool to ambient temperature and then concentrated. The residue was suspended in tetrahydrofuran (50 ml). 2-Ethyl-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)-6-methylaniline (preparation as described in WO 08/074427) (10 g, 28.3 mmol) was dissolved in tetrahydrofuran (50 ml) and pyridine (6.8 ml, 84.9 mmol) was added. The reaction mixture was stirred at ambient temperature for 3 hours, then at reflux for 3 hours. The reaction was quenched by addition of saturated aqueous sodium hydrogen carbonate (100 ml) and the mixture extracted twice with ethyl acetate (2×200 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 4:1 to 0:1) to give N-[2-ethyl-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)-6-methylphenyl]-2-fluoro-3-nitrobenzamide (6.32 g, 43% yield).

1. temperatureheated
2. temperatureto reflux for 3 hours
3. temperatureto cool to ambient temperature
4. concentrationconcentrated
5. stirringThe reaction mixture was stirred at ambient temperature for 3 hours
6. temperatureat reflux for 3 hours
7. customThe reaction was quenched by addition of saturated aqueous sodium hydrogen carbonate (100 ml)
8. extractionthe mixture extracted twice with ethyl acetate (2×200 ml)
9. dry with materialThe combined organic extracts were dried over sodium sulfate
10. concentrationconcentrated
11. customThe residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 4:1 to 0:1)