反应详情

温度

0 °C

At −78° C., diisobutylaluminum hydride (a 1M hexane solution; 1.92 ml) was added dropwise to a methylene chloride (10 ml) solution of methyl 2,5-dichloronicotinate (188 mg, 0.912 mmol). The resulting mixture was stirred at 0° C. for 30 minutes. The reaction mixture was added with brine, and the mixture was filtered through Celite. The filtrate was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a silica gel column, and the fraction obtained from the hexane:ethyl acetate (=3:1) eluate was concentrated under reduced pressure. To a chloroform (10 ml) solution of the residue (128 mg) was added thionyl chloride (0.26 ml, 3.60 mmol), followed by stirring at 50° C. for 6.5 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in butanol (10 ml). To the resulting solution were added sodium 4-chlorobenzenesulfinate (171 mg, 0.863 mmol) and potassium acetate (212 mg, 2.16 mmol) and the mixture was stirred at 70° C. for 19 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. Ethyl acetate was added to the residue, followed by successive washing with water and brine and drying over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The resulting solid was washed with hexane-diisopropyl ether, and collected by filtration, whereby the title compound (108 mg, 35%) was obtained as a white powder.

1. customAt −78° C.
2. filtrationthe mixture was filtered through Celite
3. dry with materialThe filtrate was dried over anhydrous sodium sulfate
4. filtrationAfter filtration
5. concentrationthe filtrate was concentrated under reduced pressure
6. customthe fraction obtained from the hexane
7. concentrationethyl acetate (=3:1) eluate was concentrated under reduced pressure
8. stirringby stirring at 50° C. for 6.5 hours
9. temperatureAfter cooling to room temperature
10. concentrationthe reaction mixture was concentrated under reduced pressure
11. dissolutionThe residue was dissolved in butanol (10 ml)
12. stirringthe mixture was stirred at 70° C. for 19 hours
13. temperatureAfter cooling to room temperature
14. concentrationthe reaction mixture was concentrated under reduced pressure
15. additionEthyl acetate was added to the residue
16. washby successive washing with water and brine
17. dry with materialdrying over anhydrous sodium sulfate
18. filtrationAfter filtration
19. concentrationthe filtrate was concentrated under reduced pressure
20. washThe resulting solid was washed with hexane-diisopropyl ether
21. filtrationcollected by filtration, whereby the title compound (108 mg, 35%)
22. customwas obtained as a white powder