反应详情

To a suspension of 4-cyano-3-nitrobenzoic acid (prepared as described in WO 2008/074427) (30 g, 156 mmol) in dichloromethane (150 ml) was added oxalyl chloride (15.88 ml, 187 mmol) at ambient temperature, followed by N,N-dimethylformamide (“DMF”) (0.2 ml). The reaction mixture was stirred for 30 minutes at ambient temperature and then heated to reflux for 30 minutes. The reaction mixture was allowed to cool to ambient temperature, concentrated and the residue was suspended in tetrahydrofuran (150 ml). A solution of 2,6-dibromo-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)-phenylamine (Example 3.2) (55 g, 117.3 mmol) in a mixture of tetrahydrofuran (150 ml) and pyridine (12.57 ml, 156.4 mmol) was cooled to 0° C. and the solution of 4-cyano-3-nitrobenzoyl chloride was added. The reaction mixture was stirred at ambient temperature for 12 hours. Satruated aqueous sodium hydrogen carbonate (300 ml) was added and the organic phase 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 give 4-cyano-N-[2,6-dibromo-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)phenyl]-3-nitrobenzamide (28 g, 37% yield). LC-MS (Method 2): RT=2.24, [M−H]−=642.

1. temperatureheated
2. temperatureto reflux for 30 minutes
3. temperatureto cool to ambient temperature
4. concentrationconcentrated
5. temperaturewas cooled to 0° C.
6. stirringThe reaction mixture was stirred at ambient temperature for 12 hours
7. extractionthe organic phase extracted twice with ethyl acetate (2×200 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 4:1)