反应详情

To a solution of 2,6-dichloro-3-fluoro-4-(1,2,2,2-tetrafluoro-1-trifluoromethylethyl)-phenylamine (Example 3.2) (3.48 g, 10 mmol) and 4-cyano-3-nitrobenzoic acid (made as in WO 2008/074427) (3.84 g, 20 mmol) in dichloromethane (40 ml) was added pyridine (4.17 ml, 30 mmol) and bis(2-oxo-3-oxazolidinyl)phosphonic chloride (“BOP-Cl”) (5.09 g, 20 mmol). The reaction mixture was heated to reflux for 6 hours. The reaction mixture was cooled to ambient temperature and quenched by addition of aqueous hydrochloric acid (1N) (50 ml). The mixture was then extracted three times with dichloromethane. The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate, dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent:cyclohexane/ethyl acetate 7:3) to give 4-cyano-N-[2,6-dichloro-3-fluoro-4-(1,2,2,2-tetrafluoro-1-trifluoromethylethyl)phenyl]-3-nitrobenzamide (4.76 g, 91% yield). LC-MS (Method 2): RT=2.08, [M−H]−=520.

1. temperatureThe reaction mixture was heated
2. temperatureto reflux for 6 hours
3. customquenched by addition of aqueous hydrochloric acid (1N) (50 ml)
4. extractionThe mixture was then extracted three times with dichloromethane
5. washThe combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate
6. dry with materialdried over sodium sulfate
7. concentrationconcentrated
8. customThe residue was purified by column chromatography on silica gel (eluent:cyclohexane/ethyl acetate 7:3)