反应详情

To a solution of 3-[1-(4-methylphenylsulfonyl)-piperidin-4-yl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-one (3.25 g) in dimethyl carbonate (50 ml) was added at room temperature sodium methoxide (2.21 g), and the mixture was refluxed for 4.5 hours and cooled to room temperature. To the mixture was added 1N hydrochloric acid (100 ml), and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried with magnesium sulfate. Under reduced pressure, the mixture was concentrated to give crude product (3.91 g). The resulting crude product was dissolved in THF (150 ml), and to the mixture was added at -40° C. a solution of sodium boro hydride (0.31 g) in methanol (10 ml). The mixture was stirred at -10 to -20° C. for 1 hour. To the mixture was added a solution of sodium boro hydride (0.31 g) in methanol (10 ml), and the mixture was stirred for 1.5 hours. To the mixture was added acetone (2 ml), and the mixture was stirred for 30 minutes. To the mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried with magnesium sulfate. Under reduced pressure, the mixture was concentrated, and the residue was dissolved in THF (40 ml). To the mixture was added triethylamine (3.42 ml). To the mixture was added at 0° C. methanesulfonyl chloride (0.95 ml), and the mixture was stirred at 0° C. for 30 minutes and then at room temperature for 30 minutes. To the mixture was added 1,8-diazabicyclo[5,4,0]-7-undecene (3.7 ml), and the mixture was stirred for 14 hours. To the mixture was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried with magnesium sulfate. Under reduced pressure, the mixture was concentrated, and the residue was purified with column chromatography (ethyl acetate/hexane=1:2) to give colorless crystals of methyl 4-[1-(4-methylphenylsulfonyl)piperidin-4-yl]-6,7-dihydro-5H-benzocyclo-heptene-8-carboxylate (2.01 g).

1. temperaturethe mixture was refluxed for 4.5 hours
2. extractionthe mixture was extracted with ethyl acetate
3. washThe organic layer was washed with saturated brine
4. dry with materialdried with magnesium sulfate
5. concentrationUnder reduced pressure, the mixture was concentrated
6. customto give crude product (3.91 g)
7. stirringthe mixture was stirred for 1.5 hours
8. stirringthe mixture was stirred for 30 minutes
9. extractionthe mixture was extracted with ethyl acetate
10. washThe organic layer was washed with saturated brine
11. dry with materialdried with magnesium sulfate
12. concentrationUnder reduced pressure, the mixture was concentrated
13. dissolutionthe residue was dissolved in THF (40 ml)
14. additionTo the mixture was added triethylamine (3.42 ml)
15. additionTo the mixture was added at 0° C. methanesulfonyl chloride (0.95 ml)
16. stirringthe mixture was stirred at 0° C. for 30 minutes
17. waitat room temperature for 30 minutes
18. additionTo the mixture was added 1,8-diazabicyclo[5,4,0]-7-undecene (3.7 ml)
19. stirringthe mixture was stirred for 14 hours
20. additionTo the mixture was added
21. extractionthe mixture was extracted with ethyl acetate
22. washThe organic layer was washed with saturated brine
23. dry with materialdried with magnesium sulfate
24. concentrationUnder reduced pressure, the mixture was concentrated
25. customthe residue was purified with column chromatography (ethyl acetate/hexane=1:2)