Sodium hydride → 6-(benzofuran-2-yl)-4-hydroxy-3-methyl-5-n-pentyl-2H-pyran-2-one

온도

0 °C

A solution of methyl 2-methyl-3-oxononanoate (3.06 g) in THF (5 ml) was added to a suspension of 60% NaH (608 mg) in THF (30 ml) while cooling on ice, and the mixture was stirred at 0° C. for 10 minutes and then at room temperature for 30 minutes. The reaction solution was cooled to −78° C., 1.66 M n-BuLi (9.2 ml) was added, and the mixture was stirred at −78° C. for 30 minutes to prepare a dienolate. A solution of methyl 2-benzofurancarboxylate (1.25 g) in THF (5 ml) was added to the dienolate, and the mixture was stirred at −78° C. for 30 minutes. The reaction solution was brought to 0° C., an NH4Cl aqueous solution was added for quenching, and extraction was performed with AcOEt. The organic layer was rinsed with water and saturated saline in that order, and then dried with Na2SO4, filtered and concentrated. The residue was dissolved in MeOH (50 ml), and after adding 2N-LiOH (30 ml) and stirring at room temperature for 2 hours, 1N-HCl was added at 0° C. to acidity of approximately pH 3, and extraction was performed with AcOEt. The organic layer was rinsed with water and saturated saline in that order, and then dried with Na2SO4, filtered and concentrated. Pyridine (20 ml) and Ac2O (20 ml) were added to the residue, and after stirring the mixture at room temperature for 5 hours it was concentrated under reduced pressure. The residue was dissolved in MeOH (20 ml), imidazole (483 mg) was added at 0° C., and after stirring the mixture at 0° C. for 10 minutes and then at room temperature for 30 minutes, it was concentrated under reduced pressure. AcOEt was added to the residue, and the precipitated crystals were filtered off. The crystals were recrystallized from EtOH to obtain 6-(benzofuran-2-yl)-4-hydroxy-3-methyl-5-n-pentyl-2H-pyran-2-one.

1. temperaturewhile cooling on ice
2. waitat room temperature for 30 minutes
3. temperatureThe reaction solution was cooled to −78° C.
4. stirringthe mixture was stirred at −78° C. for 30 minutes
5. customto prepare a dienolate
6. stirringthe mixture was stirred at −78° C. for 30 minutes
7. customwas brought to 0° C.
8. customfor quenching
9. extractionextraction
10. washThe organic layer was rinsed with water and saturated saline in that order
11. dry with materialdried with Na2SO4
12. filtrationfiltered
13. concentrationconcentrated
14. dissolutionThe residue was dissolved in MeOH (50 ml)
15. additionafter adding 2N-LiOH (30 ml)
16. stirringstirring at room temperature for 2 hours
17. addition1N-HCl was added at 0° C. to acidity of approximately pH 3, and extraction
18. washThe organic layer was rinsed with water and saturated saline in that order
19. dry with materialdried with Na2SO4
20. filtrationfiltered
21. concentrationconcentrated
22. additionPyridine (20 ml) and Ac2O (20 ml) were added to the residue
23. stirringafter stirring the mixture at room temperature for 5 hours it
24. concentrationwas concentrated under reduced pressure
25. dissolutionThe residue was dissolved in MeOH (20 ml)
26. additionimidazole (483 mg) was added at 0° C.
27. stirringafter stirring the mixture at 0° C. for 10 minutes
28. waitat room temperature for 30 minutes
29. concentrationit was concentrated under reduced pressure
30. additionAcOEt was added to the residue
31. filtrationthe precipitated crystals were filtered off
32. customThe crystals were recrystallized from EtOH

ORD 기록

ord-378c80784fc54a988e6d162dec66bc09

출처 데이터셋

uspto-grants-2003_07

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06589984B1