反应详情

温度

50 °C

To a solution of 4-bromo-2-fluorophenol (2.0 g) in acetone (40 ml) were sequentially added potassium carbonate (2.0 g) and benzyl bromide (1.5 ml), and the solution was stirred for 2 hours at 50° C. Water was added thereto followed by stirring, the solution was extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, then the solvent was evaporated in vacuo. A suspension of the resulting 1-benzyloxy-4-bromo-2-fluorobenzene (3.3 g), (trimethylsilyl)acetylene (1.5 g), dichlorobis(triphenylphosphine)palladium(II) (370 mg) and copper(I) iodide (50 mg) in triethylamine (30 ml) and pyridine (15 ml) was stirred for 1.5 hours at 80° C. under a nitrogen atmosphere. The insoluble material was removed by filtration, then the filtrate was neutralized with 5N hydrochloric acid. The solution was extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, then the solvent was evaporated in vacuo. To the resulting residue were sequentially added methanol (40 ml) and an aqueous solution of 2N sodium hydroxide (5 ml), the solution was stirred for 45 minutes at 80° C., and then neutralized with 1N hydrochloric acid. The solution was extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, and then the solvent was evaporated in vacuo. The residue was purified by NH silica gel column chromatography (hexane-ethyl acetate system) to provide the title compound (2.2 g).

1. stirringby stirring
2. extractionthe solution was extracted with ethyl acetate
3. washsequentially washed with water and brine
4. dry with materialdried over anhydrous magnesium sulfate
5. customthe solvent was evaporated in vacuo
6. additionA suspension of the resulting 1-benzyloxy-4-bromo-2-fluorobenzene (3.3 g), (trimethylsilyl)acetylene (1.5 g), dichlorobis(triphenylphosphine)palladium(II) (370 mg) and copper(I) iodide (50 mg) in triethylamine (30 ml) and pyridine (15 ml)
7. stirringwas stirred for 1.5 hours at 80° C. under a nitrogen atmosphere
8. customThe insoluble material was removed by filtration
9. extractionThe solution was extracted with ethyl acetate
10. washsequentially washed with water and brine
11. dry with materialdried over anhydrous magnesium sulfate
12. customthe solvent was evaporated in vacuo
13. stirringan aqueous solution of 2N sodium hydroxide (5 ml), the solution was stirred for 45 minutes at 80° C.
14. extractionThe solution was extracted with ethyl acetate
15. washsequentially washed with water and brine
16. dry with materialdried over anhydrous magnesium sulfate
17. customthe solvent was evaporated in vacuo
18. customThe residue was purified by NH silica gel column chromatography (hexane-ethyl acetate system)