反应详情

To a mixture of methyl(4-(difluoromethyl)-6-hydroxy-1-benzothiophen-3-yl)acetate (78 mg) and THF (dry) (2 mL) were added (2,6-dimethylpyridin-3-yl)methanol (43.2 mg), tri-n-butylphosphine (0.212 mL) and ADDP (94 mg) at room temperature. The mixture was stirred at room temperature for 2 h. To the mixture were added ADDP (94 mg) and tri-n-butylphosphine (0.212 mL), and the mixture was stirred at room temperature for 30 min. The insoluble material was removed by filtration, and the filtrate was concentrated in vacuo. The residue was purified by short pad of silica gel (EtOAc/hexane). To a mixture of the residue and THF (2 mL) was added 1N NaOH (1 mL) at room temperature. The mixture was stirred at room temperature for 16 h. The mixture was neutralized with 1N HCl at room temperature and extracted with EtOAc. The organic layer was separated, washed successively with water and brine, dried over MgSO4 and concentrated in vacuo. The crude product was purified by preparative HPLC (C18, H2O/CH3CN (including 10 mM NH4HCO3)). The fraction was extracted with EtOAc. The organic layer was separated, washed successively with water and brine, dried over MgSO4 and concentrated in vacuo. The residue was crystallized from EtOAc-hexane to give the title compound (29.1 mg).

1. stirringthe mixture was stirred at room temperature for 30 min
2. customThe insoluble material was removed by filtration
3. concentrationthe filtrate was concentrated in vacuo
4. customThe residue was purified by short pad of silica gel (EtOAc/hexane)
5. additionTo a mixture of the residue and THF (2 mL)
6. additionwas added 1N NaOH (1 mL) at room temperature
7. stirringThe mixture was stirred at room temperature for 16 h
8. customwas neutralized with 1N HCl at room temperature
9. extractionextracted with EtOAc
10. customThe organic layer was separated
11. washwashed successively with water and brine
12. dry with materialdried over MgSO4
13. concentrationconcentrated in vacuo
14. customThe crude product was purified by preparative HPLC (C18, H2O/CH3CN (including 10 mM NH4HCO3))
15. extractionThe fraction was extracted with EtOAc
16. customThe organic layer was separated
17. washwashed successively with water and brine
18. dry with materialdried over MgSO4
19. concentrationconcentrated in vacuo
20. customThe residue was crystallized from EtOAc-hexane