反应详情

46 mg of triethylamine and 39 mg of methanesulfonyl chloride were added to a chloroform (5 ml) solution of 100 mg of N-(4-(4-((t-butyl(dimethyl)silyl)oxy)-2-fluoro-1-hydroxybutyl)-3-fluorophenyl)pyridine-2-carboxamide, and the reaction liquid was stirred at room temperature for 30 minutes. Aqueous saturated sodium bicarbonate was added to the reaction liquid, extracted with chloroform, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 22 mg of sodium azide was added to a dimethylformamide (4 ml) solution of the resulting residue, and the reaction liquid was stirred at 40° C. for 2 hours. The reaction liquid was cooled, water was added to it, extracted with ethyl acetate, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 0.3 ml of tetrabutylammonium fluoride (1.0 M tetrahydrofuran solution) was added to a tetrahydrofuran (4 ml) solution of the resulting residue, and the reaction liquid was stirred at room temperature for 1 hour. Water was added to the reaction liquid, extracted with ethyl acetate, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 46 mg of triethylamine and 39 mg of methanesulfonyl chloride were added in order to a chloroform (5 ml) solution of the resulting residue, and the reaction liquid was stirred at room temperature for 30 minutes. Aqueous saturated sodium bicarbonate was added to the reaction liquid, extracted with ethyl acetate, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 10 mg of copper sulfate pentahydrate and 50 mg of sodium borohydride were added in order to a methanol (4 ml) solution of the resulting residue, and the reaction liquid was stirred at 40° C. for 1 hour. The reaction liquid was cooled, aqueous saturated sodium bicarbonate was added to it, extracted with chloroform, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 46 mg of triethylamine, 35 mg of acetic anhydride and 5 mg of N,N-4-dimethylaminopyridine were added in order to a chloroform (4 ml) solution of the resulting residue, and the reaction liquid was stirred at room temperature for 30 minutes. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through partitioning thin-layer chromatography (chloroform/methanol=30/1) to obtain a diastereomer A and a diastereomer B of the entitled compound each as a colorless oily substance.

1. customthe reaction liquid
2. extractionextracted with chloroform
3. dry with materialdried with anhydrous sodium sulfate
4. customThe solvent was evaporated away under reduced pressure, and 22 mg of sodium azide
5. additionwas added to a dimethylformamide (4 ml) solution of the resulting residue
6. customthe reaction liquid
7. stirringwas stirred at 40° C. for 2 hours
8. customThe reaction liquid
9. temperaturewas cooled
10. extractionextracted with ethyl acetate
11. dry with materialdried with anhydrous sodium sulfate
12. customThe solvent was evaporated away under reduced pressure, and 0.3 ml of tetrabutylammonium fluoride (1.0 M tetrahydrofuran solution)
13. additionwas added to a tetrahydrofuran (4 ml) solution of the resulting residue
14. customthe reaction liquid
15. stirringwas stirred at room temperature for 1 hour
16. extractionextracted with ethyl acetate
17. dry with materialdried with anhydrous sodium sulfate
18. customThe solvent was evaporated away under reduced pressure, and 46 mg of triethylamine and 39 mg of methanesulfonyl chloride
19. additionwere added in order to a chloroform (5 ml) solution of the resulting residue
20. customthe reaction liquid
21. stirringwas stirred at room temperature for 30 minutes
22. extractionextracted with ethyl acetate
23. dry with materialdried with anhydrous sodium sulfate
24. customThe solvent was evaporated away under reduced pressure, and 10 mg of copper sulfate pentahydrate and 50 mg of sodium borohydride
25. additionwere added in order to a methanol (4 ml) solution of the resulting residue
26. customthe reaction liquid
27. stirringwas stirred at 40° C. for 1 hour
28. customThe reaction liquid
29. temperaturewas cooled
30. extractionextracted with chloroform
31. dry with materialdried with anhydrous sodium sulfate
32. customThe solvent was evaporated away under reduced pressure, and 46 mg of triethylamine, 35 mg of acetic anhydride and 5 mg of N,N-4-dimethylaminopyridine
33. additionwere added in order to a chloroform (4 ml) solution of the resulting residue
34. customthe reaction liquid
35. stirringwas stirred at room temperature for 30 minutes
36. customThe solvent was evaporated away under reduced pressure
37. customthe resulting residue was purified
38. customthrough partitioning thin-layer chromatography (chloroform/methanol=30/1)
39. customto obtain a diastereomer A