反应详情

To a solution (5 mL) of tert-butyl {[1-(6-chloro-5-methyl-3-pyridinesulfonyl)-5-phenyl-1H-pyrrol-3-yl]methyl}methylcarbamate (237 mg) in tetrahydrofuran was added hydrazine (160 mg) at room temperature with stirring. After stirring at the same temperature for 3 hr, a saturated aqueous sodium hydrogencarbonate solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (30 mL), manganese dioxide (75% chemically treated product, 1.0 g) was added, and the mixture was stirred at room temperature for 10 min. The reaction mixture was filtered through celite, and celite was washed with ethyl acetate. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1→1:1) to give an oil. The obtained oil was dissolved in ethanol (2 mL), and a 4 mol/L hydrogen chloride-ethyl acetate solution (1 mL) was added. After stirring at room temperature for 2 hr, the solvent was evaporated under reduced pressure, a saturated aqueous sodium hydrogencarbonate solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue (93 mg) was dissolved in ethanol (3 mL), and fumaric acid (29 mg) was added. After allowing to stand at room temperature for 30 min, the precipitated crystals were collected by filtration and washed with methanol to give the title compound as a colorless solid (yield 91 mg, 40%).

1. stirringAfter stirring at the same temperature for 3 hr
2. extractionthe mixture was extracted with ethyl acetate
3. washThe extract was washed with water and saturated brine
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationconcentrated under reduced pressure
6. dissolutionThe residue was dissolved in tetrahydrofuran (30 mL)
7. additionmanganese dioxide (75% chemically treated product, 1.0 g) was added
8. stirringthe mixture was stirred at room temperature for 10 min
9. filtrationThe reaction mixture was filtered through celite, and celite
10. washwas washed with ethyl acetate
11. concentrationThe filtrate was concentrated under reduced pressure
12. customthe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1→1:1)
13. customto give an oil
14. stirringAfter stirring at room temperature for 2 hr
15. customthe solvent was evaporated under reduced pressure
16. additiona saturated aqueous sodium hydrogencarbonate solution was added
17. extractionthe mixture was extracted with ethyl acetate
18. washThe extract was washed with water and saturated brine
19. dry with materialdried over anhydrous magnesium sulfate
20. concentrationconcentrated under reduced pressure
21. dissolutionThe residue (93 mg) was dissolved in ethanol (3 mL)
22. additionfumaric acid (29 mg) was added
23. filtrationthe precipitated crystals were collected by filtration
24. washwashed with methanol