反应详情

2-[3,5-Bis(methoxymethoxy)-2-iodo-6-(4-methoxy-benzoyl)phenyl]-N-(2-hydroxyethyl)-N-(2-methoxyethyl)acetamide (0.56 g, 0.91 mmol) obtained in Example 135, Step 2 was dissolved in toluene (10 mL), and ethoxyvinyl tributyltin (0.46 mL, 1.4 mmol) and bis(triphenylphosphine)palladium (II) dichloride (0.05 g, 0.071 mmol) were successively added thereto in an atmosphere of argon. The reaction mixture was stirred for 3 hours under heating and reflux, and then cooled to room temperature. To the mixture was added a saturated aqueous solution of ammonium fluoride, followed by stirring at room temperature for 6 hours. The reaction mixture was filtered through Celite, and the resulting filtrate was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The resulting residue was dissolved in tetrahydrofuran (10 mL), and a 1 mol/L hydrochloric acid was added thereto with stirring under ice-cooling, followed by stirring at room temperature for 1 hour. The reaction mixture was ice-cooled and neutralized with a saturated aqueous solution of sodium hydrogencarbonate, followed by liquid separation. After the aqueous layer was extracted with ethyl acetate, the organic layers were combined, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (20 mL), and activated carbon (400 mg) was added thereto, followed by stirring at room temperature for 15 hours. The reaction mixture was filtered through Celite, and the obtained filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate/methanol=10/0-9/1 to obtain 2-[2-acetyl-3,5-bis(methoxymethoxy)-6-(4-methoxybenzoyl)phenyl]-N-(2-hydroxyethyl)-N-(2-methoxyethyl)acetamide (0.25 g, 51%).

1. temperatureunder heating
2. temperaturereflux
3. stirringby stirring at room temperature for 6 hours
4. filtrationThe reaction mixture was filtered through Celite
5. extractionthe resulting filtrate was extracted with ethyl acetate
6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
7. concentrationconcentrated under reduced pressure
8. dissolutionThe resulting residue was dissolved in tetrahydrofuran (10 mL)
9. additiona 1 mol/L hydrochloric acid was added
10. stirringwith stirring under ice-
11. temperaturecooling
12. stirringby stirring at room temperature for 1 hour
13. temperaturecooled
14. customfollowed by liquid separation
15. extractionAfter the aqueous layer was extracted with ethyl acetate
16. dry with materialdried over anhydrous sodium sulfate
17. concentrationconcentrated under reduced pressure
18. dissolutionThe resulting residue was dissolved in ethyl acetate (20 mL)
19. additionactivated carbon (400 mg) was added
20. stirringby stirring at room temperature for 15 hours
21. filtrationThe reaction mixture was filtered through Celite
22. concentrationthe obtained filtrate was concentrated under reduced pressure
23. customThe resulting residue was purified by silica gel column chromatography (ethyl acetate/methanol=10/0-9/1