反应详情

温度

60 °C

To a solution of methyl 7-hydroxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indole-2-carboxylate (2.5 g), tributylphosphine (2.79 g) and 1-methoxypropan-2-ol (1.24 g) in tetrahydrofuran (50 mL) was added 1,1′-(azodicarbonyl)dipiperidine (3.48 g) at 60° C. The whole was stirred at 60° C. for 1.5 h and then concentrated in vacuo. Diisopropyl ether was added to the residue and insoluble materials were removed by filtration. The filtrate was concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate:hexane=1:2 to 2:1, volume ratio) and then by basic silica gel chromatography (ethyl acetate:hexane=1:2 to 2:1, volume ratio) to give a colorless oil. A mixture of the oil, 1M aqueous sodium hydroxide solution (15 mL), tetrahydrofuran (15 mL) and methanol (15 mL) was stirred at room temperature for 20 h. The mixture was washed with diethyl ether. The organic layer was extracted with 1M aqueous sodium hydroxide solution. The water layers were combined, acidified by 1M hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSO4), filtered, and concentrated in vacuo. The residue was washed with hexane to give the title compound (1.50 g, 52%) as colorless crystals. MS 421 (MH+).

1. concentrationconcentrated in vacuo
2. additionDiisopropyl ether was added to the residue and insoluble materials
3. customwere removed by filtration
4. concentrationThe filtrate was concentrated in vacuo
5. customThe residue was purified by silica gel chromatography (ethyl acetate:hexane=1:2 to 2:1, volume ratio)
6. customby basic silica gel chromatography (ethyl acetate:hexane=1:2 to 2:1, volume ratio) to give a colorless oil
7. stirringwas stirred at room temperature for 20 h
8. washThe mixture was washed with diethyl ether
9. extractionThe organic layer was extracted with 1M aqueous sodium hydroxide solution
10. extractionextracted with ethyl acetate
11. washThe organic layer was washed with brine
12. dry with materialdried (MgSO4)
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. washThe residue was washed with hexane