反应详情

温度

80 °C

Bromoacetaldehyde dimethyl acetal (1.17 mL, 10.0 mmol) and a catalytic amount of sodium iodide were added to a solution (25 mL) of 2-bromo-4-fluorophenol (0.548 mL, 5.00 mmol) and potassium carbonate (1.38 g, 10.0 mmol) in DMF, and stirred at 80° C. overnight. The solvent was distilled away under reduced pressure. The residue was diluted with ethyl acetate, washed with water and saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane/ethyl acetate). The resulting compound (1.12 g, 4.01 mmol) was dissolved in chlorobenzene (5 mL), and added at 120° C. to a solution (5 mL) of a polyphosphoric acid (1.5 g) in chlorobenzene. After the reaction solution was stirred at 120° C. overnight, the solvent was distilled away under reduced pressure. To the residue, ethyl acetate and water were added. Under ice-cooling, this was poured into a 1 N sodium hydroxide aqueous solution, and stirred. After that, the insoluble material was filtered off, and extraction was performed with ethyl acetate. The organic phase was washed with saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane) to thus obtain the title compound.

1. distillationThe solvent was distilled away under reduced pressure
2. additionThe residue was diluted with ethyl acetate
3. washwashed with water and saturated brine
4. dry with materialdried over anhydrous magnesium sulfate
5. distillationThe solvent was distilled away under reduced pressure
6. customThe resulting residue was purified by silica gel chromatography (hexane/ethyl acetate)
7. stirringAfter the reaction solution was stirred at 120° C. overnight
8. distillationthe solvent was distilled away under reduced pressure
9. additionTo the residue, ethyl acetate and water were added
10. temperatureUnder ice-cooling
11. additionthis was poured into a 1 N sodium hydroxide aqueous solution
12. stirringstirred
13. filtrationAfter that, the insoluble material was filtered off
14. extractionextraction
15. washThe organic phase was washed with saturated brine
16. dry with materialdried over anhydrous magnesium sulfate
17. distillationThe solvent was distilled away under reduced pressure
18. customThe resulting residue was purified by silica gel chromatography (hexane)