反应详情

温度

80 °C

A solution of methyl 2-(2-bromo-4-chlorophenoxy)propanoate (Intermediate 263 ; 130 mg; 0.44 mmol), 2-ethynyl-1-fluoro-4-(propane-1-sulfonyl)-benzene (Intermediate 109 ; 110 mg; 0.49 mmol), bis(triphenylphosphine)palladium (II) chloride (9.3 mg; 0.01 mmol), triphenylphosphine (23.2 mg; 0.09 mmol) and cuprous iodide (2.5 mg; 0.01 mmol) in TEA (985 μl) was degassed with nitrogen. The reaction mixture was heated overnight at 80° C., diluted with EtOAc and washed with sat. ammonium chloride solution and brine. The organic phase was dried over MgSO4, filtered and concentrated to dryness affording a dark brown sticky solid, which was purified by flash column chromatography (silica), eluting with cyclohexane containing increasing amounts of EtOAc. The intermediate thus obtained was dissolved in a mixture of dioxane (2.6 ml) and water (2.6 ml) and treated with a 4 N solution of HCl in dioxane (1.33 ml). After heating at 100° C. for 16 hours, water was added and the reaction mixture was extracted 3 times with EtOAC. The organic phase was dried over MgSO4, filtered and concentrated to dryness affording a yellow sticky solid, which was triturated in diethylether/pentane to afford the title compound as a white solid.

1. washwashed with sat. ammonium chloride solution and brine
2. dry with materialThe organic phase was dried over MgSO4
3. filtrationfiltered
4. concentrationconcentrated to dryness
5. customaffording a dark brown sticky solid, which
6. customwas purified by flash column chromatography (silica)
7. washeluting with cyclohexane containing
8. temperatureincreasing amounts of EtOAc
9. customThe intermediate thus obtained
10. temperatureAfter heating at 100° C. for 16 hours
11. extractionthe reaction mixture was extracted 3 times with EtOAC
12. dry with materialThe organic phase was dried over MgSO4
13. filtrationfiltered
14. concentrationconcentrated to dryness
15. customaffording a yellow sticky solid, which
16. customwas triturated in diethylether/pentane