反应详情

温度

25 °C

A solution of the product from Example 1A (21.4 g) in dioxane (100 mL) was treated with sodium hydroxide solution (57 mL, 1N), stirred at 25° C. for 30 minutes and concentrated. The concentrate was cooled to 0° C., and acidified to pH 5 with 4N HCl. The mixture was partitioned between dichloromethane and water, and the organic phase layer was washed with brine, dried over MgSO4, filtered and concentrated. A solution of the residue in N,N-dimethylformamide (100 mL) was treated with imidazole (21 g, 308.5 mmol) and t-butyldimethylsilyl chloride (23 g, 152.6 mmol), stirred at 25° C. for 16 hours and concentrated. The residue was combined with ice and acidified with 4N HCl to pH 3. Ethyl acetate (50 mL) was added to permit stirring during the acidification. The mixture was extracted with ethyl acetate, washed with brine, dried over MgSO4, filtered, and concentrated. The residue was chromatographed on silica gel eluting with a gradient of 200%-100% ethyl acetate in chloroform, followed by elution with 5% methanol in ethyl acetate to give the title product (11.3 g, 49% yield).

1. concentrationconcentrated
2. temperatureThe concentrate was cooled to 0° C.
3. customThe mixture was partitioned between dichloromethane and water
4. washthe organic phase layer was washed with brine
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. stirringstirred at 25° C. for 16 hours
9. concentrationconcentrated
10. additionEthyl acetate (50 mL) was added
11. stirringto permit stirring during the acidification
12. extractionThe mixture was extracted with ethyl acetate
13. washwashed with brine
14. dry with materialdried over MgSO4
15. filtrationfiltered
16. concentrationconcentrated
17. customThe residue was chromatographed on silica gel eluting with a gradient of 200%-100% ethyl acetate in chloroform
18. washfollowed by elution with 5% methanol in ethyl acetate