反应详情

温度

90 °C

To the compound (300 mg, 1.4 mmol) obtained in Step 2, 4-hydroxyphenylboronic acid (230 mg, 1.7 mmol), sodium carbonate (292 mg, 2.8 mmol), tetrakis(triphenylphosphine)palladium(0) (hereinafter, Pd(PPh3)4) (catalytic amount), 1,4-dioxane (10 mL), water (3 mL) were added, and stirred at 90° C. for 2 hours. The solvent was distilled away under reduced pressure. Ethyl acetate was used as an extraction solvent, and after washing with a 1 N hydrochloric acid aqueous solution and saturated brine, the resultant was dried over magnesium sulfate. The solvent was distilled away under reduced pressure. To the resulting residue, DMF (10 ml), potassium carbonate (280 mg, 2.8 mmol), and methyl 3-(bromomethyl)benzoate (470 mg, 2.1 mmol) were added, and stirred at 50° C. overnight. Ethyl acetate was used as an extraction solvent, and after washing with water, a 1 N sodium hydroxide aqueous solution, and saturated brine, the resultant was dried over magnesium sulfate. The solvent was distilled away under reduced pressure. To the resulting residue, THF (5 mL), methanol (5 mL), and a 1 N sodium hydroxide aqueous solution (10 mL) were added, and stirred at room temperature for 4 hours. The solvent was distilled away under reduced pressure. Ethyl acetate was used as an extraction solvent, and after washing with a 1 N hydrochloric acid aqueous solution and saturated brine, the resultant was dried over magnesium sulfate. After the solvent was distilled away under reduced pressure, the resulting residue was washed with a water-acetonitrile mixture solvent, and then dried to thus obtain the title compound.

1. distillationThe solvent was distilled away under reduced pressure
2. washafter washing with a 1 N hydrochloric acid aqueous solution and saturated brine
3. dry with materialthe resultant was dried over magnesium sulfate
4. distillationThe solvent was distilled away under reduced pressure
5. stirringstirred at 50° C. overnight
6. washafter washing with water
7. dry with materiala 1 N sodium hydroxide aqueous solution, and saturated brine, the resultant was dried over magnesium sulfate
8. distillationThe solvent was distilled away under reduced pressure
9. additionTo the resulting residue, THF (5 mL), methanol (5 mL), and a 1 N sodium hydroxide aqueous solution (10 mL) were added
10. stirringstirred at room temperature for 4 hours
11. distillationThe solvent was distilled away under reduced pressure
12. washafter washing with a 1 N hydrochloric acid aqueous solution and saturated brine
13. dry with materialthe resultant was dried over magnesium sulfate
14. distillationAfter the solvent was distilled away under reduced pressure
15. washthe resulting residue was washed with a water-acetonitrile mixture solvent
16. customdried