反应详情

温度

60 °C

A solution of (2-fluoro-6-iodo-phenyl)-carbamic acid tert-butyl ester (22.5 g, 67 mmol) in ethanol (100 mL) and 48% aqueous hydrobromic acid (100 mL) was stirred at RT. After 1 h the solvent was removed under reduced pressure and the residue was resuspended in 48% aqueous hydrobromic acid (100 mL). The suspension was heated to 60° C. for 10 min followed by cooling to 0° C. in an ice-water bath. A solution of sodium nitrite (4.9 g, 70 mmol) in water (25 mL) was added dropwise keeping the internal temperature below 5° C. The resulting suspension was stirred for 15 min at 0° C. followed by addition of copper (I) bromide (2.93 g, 20 mmol). The mixture was heated to 80° C. for 1 h and subsequently cooled to RT. The mixture was extracted with dichloromethane (2×250 mL) and the organic layer was washed with brine (150 mL), 10% aqueous sodium hydroxide solution (250 mL), brine (250 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by flash column chromatography (5% ethyl acetate:hexanes) to afford 10.5 g (50%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 7.01-7.05 (m, 1H), 7.08-7.12 (m, 1H), 7.67 (d, J=4.8 Hz); 13C NMR (100 MHz, CDCl3): δ 102.5, 115.9 (d, J=22 Hz), 117.6 (d, J=21 Hz), 129.8 (d, J=14 Hz), 135.4 (d, J=21 Hz), 158.7 (d, J=250 Hz); 19F NMR (282 MHz, CDCl3): δ−96.3 (m, 1F).

1. customAfter 1 h the solvent was removed under reduced pressure
2. temperatureby cooling to 0° C. in an ice-water bath
3. customthe internal temperature below 5° C
4. temperatureThe mixture was heated to 80° C. for 1 h
5. temperaturesubsequently cooled to RT
6. extractionThe mixture was extracted with dichloromethane (2×250 mL)
7. washthe organic layer was washed with brine (150 mL), 10% aqueous sodium hydroxide solution (250 mL), brine (250 mL)
8. dry with materialdried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customThe residue was purified by flash column chromatography (5% ethyl acetate:hexanes)