反应详情

A solution of 108 ml of boron trifluoride etherate in 300 ml of dichloromethane was added dropwise to a solution of 79.3 g of 1,5,6,7-tetrahydro-1-methyl-4H-indazol-4-one and 100 g of ethyl diazoacetate in 1500 ml of dichloromethane. The rate of the addition was adjusted so that the temperature of the reaction mixture did not exceed 25° C. and the evolution of gas did not become vigorous. The addition took 3.5 hours and the reaction mixture was then stirred at room temperature, cooled to 0° C., and treated dropwise with 1000 ml of saturated aqueous sodium bicarbonate solution. The resulting slurry was stirred briefly and the layers which formed on standing were separated. The organic layer was washed with brine and dried over magnesium sulfate and the solvent was removed under reduced pressure to leave an amber oil. The oil was dissolved in dichloromethane and washed with 2.5M sodium hydroxide (two 300-ml portions). The dichloromethane solution was dried over magnesium sulfate and concentrated under reduced pressure to leave an amber oil. This oil was flash chromatographed (10% acetone in dichloromethane) to provide a further amber oil. This oil was treated with 24 g of potassium hydroxide an 300 ml of water and the mixture was heated in a boiling-water bath for 30 minutes. 5N Hydrochloric acid was added slowly until the pH was 2. The mixture was then heated briefly in a boiling-water bath and poured over ice. It was then neutralized with saturated sodium bicarbonate and extracted exhaustively with dichloromethane The combined extracts were dried over magnesium su1fate and the solvent was removed under reduced pressure to provide a dark oil which was heated at reflux with 60 ml of N,N-dimethylformamide dimethyl acetal for 2 hours. The solvent was removed under reduced pressure and the residue was flash chromatographed (10% acetone in dichloromethane) to give 5,6,7,8-tetrahydro-4(1H)-cycloheptapyrazolone as a red crystalline solid.

1. additionThe rate of the addition
2. customdid not exceed 25° C.
3. additionThe addition
4. temperaturecooled to 0° C.
5. stirringThe resulting slurry was stirred briefly
6. customthe layers which formed on standing
7. customwere separated
8. washThe organic layer was washed with brine
9. dry with materialdried over magnesium sulfate
10. customthe solvent was removed under reduced pressure
11. customto leave an amber oil
12. washwashed with 2.5M sodium hydroxide (two 300-ml portions)
13. dry with materialThe dichloromethane solution was dried over magnesium sulfate
14. concentrationconcentrated under reduced pressure
15. customto leave an amber oil
16. customchromatographed (10% acetone in dichloromethane)
17. customto provide a further amber oil
18. temperaturethe mixture was heated in a boiling-water bath for 30 minutes
19. temperatureThe mixture was then heated briefly in a boiling-water bath
20. additionpoured over ice
21. extractionextracted exhaustively with dichloromethane The combined extracts
22. dry with materialwere dried over magnesium su1fate
23. customthe solvent was removed under reduced pressure
24. customto provide a dark oil which
25. temperaturewas heated
26. customThe solvent was removed under reduced pressure
27. customchromatographed (10% acetone in dichloromethane)