反应详情

4-Benzyloxy-1-bromo-2-fluorobenzene (3.55 g, 12.6 mmol), 4-(4-trifluoromethoxyphenoxy)piperidine (3.0 g, 11.5 mmol), sodium tert-butoxide (1.55 g, 16.1 mmol) and toluene (60 ml) were mixed. Palladium acetate (0.10 g, 0.46 mmol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.57 g, 0.92 mmol) were added thereto. The mixture was heated and refluxed under a nitrogen atmosphere for 4 hours. A saturated ammonium chloride aqueous solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution and dried over sodium sulfate. After filtering, the filtrate was concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (hexane:ethyl acetate=80:20→60:40), and the resulting crude crystal was washed with hexane-diethylether to afford the title compound as a white powder (3.76 g, yield 71%).

1. temperatureThe mixture was heated
2. temperaturerefluxed under a nitrogen atmosphere for 4 hours
3. extractionfollowed by extraction with ethyl acetate
4. washThe organic layer was washed with a saturated sodium chloride aqueous solution
5. dry with materialdried over sodium sulfate
6. filtrationAfter filtering
7. concentrationthe filtrate was concentrated under reduced pressure
8. customThe residue thus obtained
9. customwas purified by silica gel column chromatography (hexane:ethyl acetate=80:20→60:40)
10. washthe resulting crude crystal was washed with hexane-diethylether