反应详情

Under ice-cooling, pyridine (0.30 mL) and acetic anhydride (6.7 μL) were sequentially added to a methylene chloride (1 mL) suspension of 2-(2-hydroxy-5-(piperidin-4-yloxy)benzamido)-4-phenylbenzoic acid hydrochloride (0.030 g), followed by stirring at room temperature for 1 hour. Pyridine (0.20 mL) and acetic anhydride (5.4 μL) were sequentially added to the reaction mixture, followed by stirring at room temperature for 1 hour and 30 minutes. The solvent was evaporated under reduced pressure, and methanol (0.5 mL) and a 2 mol/L aqueous solution of sodium hydroxide (0.19 mL) were added to the residue, followed by stirring at room temperature for 1 hour. To the reaction mixture, 1 mol/L hydrochloric acid (5 mL) and ethyl acetate were added. The organic layer was separated, washed with 1 mol/L hydrochloric acid, water, and a saturated aqueous solution of sodium chloride sequentially, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. Dioxane (0.5 mL), methanol (0.5 mL), and a 2 mol/L aqueous solution of sodium hydroxide (0.32 mL) were added to the obtained residue, followed by stirring at 70° C. for 30 minutes. After cooling the reaction mixture to room temperature, the solvent was evaporated under reduced pressure, and water was added to the obtained residue. After adjusting the pH to 3 with 6 mol/L hydrochloric acid, the solid substance was collected by filtration to obtain 0.022 g of 2-(5-(1-acetylpiperidin-4-yloxy)-2-hydroxybenzamido)-4-phenylbenzoic acid as a white solid.

1. temperatureUnder ice-cooling
2. stirringby stirring at room temperature for 1 hour and 30 minutes
3. customThe solvent was evaporated under reduced pressure, and methanol (0.5 mL)
4. additiona 2 mol/L aqueous solution of sodium hydroxide (0.19 mL) were added to the residue
5. stirringby stirring at room temperature for 1 hour
6. additionTo the reaction mixture, 1 mol/L hydrochloric acid (5 mL) and ethyl acetate were added
7. customThe organic layer was separated
8. washwashed with 1 mol/L hydrochloric acid, water
9. dry with materiala saturated aqueous solution of sodium chloride sequentially, and dried over anhydrous magnesium sulfate
10. customthe solvent was evaporated under reduced pressure
11. additionDioxane (0.5 mL), methanol (0.5 mL), and a 2 mol/L aqueous solution of sodium hydroxide (0.32 mL) were added to the obtained residue
12. stirringby stirring at 70° C. for 30 minutes
13. temperatureAfter cooling the reaction mixture to room temperature
14. customthe solvent was evaporated under reduced pressure, and water
15. additionwas added to the obtained residue
16. filtrationthe solid substance was collected by filtration