反应详情

To a solution of ethyl [4-(cyclopropylsulfonyl)phenyl](oxo)acetate (20.1 g) in a mixed solvent of tetrahydrofuran (140 mL) and methanol (70 mL) was added 2M aqueous sodium hydroxide solution (70 mL), and the mixture was stirred at room temperature for 16 hr. The reaction mixture was acidified with 1M hydrochloric acid and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was cooled to −78° C., hydrazine monohydrate (17.3 mL) was added, and the mixture was warmed to room temperature by stirring. The reaction mixture was stirred at 80° C. for 10 min and cooled to room temperature. Potassium hydroxide (12.0 g) was added to the reaction mixture, and the mixture was stirred at 100° C. for 16 hr. Water was added to the reaction mixture, and the aqueous layer was washed with diethyl ether. The aqueous layer was acidified with 1M hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To a solution of the residue in ethanol (500 mL) was added thionyl chloride (6.23 mL) under ice-cooling, and the mixture was warmed to room temperature and stirred at room temperature for 16 hr. The reaction mixture was concentrated under reduced pressure, and the residue was recrystallized from hexane-ether to give the title compound (13.7 g, yield 72%) as colorless crystals. melting point 102-104° C.

1. extractionextracted with ethyl acetate
2. washThe extract was washed with saturated brine
3. dry with materialdried over anhydrous sodium sulfate
4. concentrationconcentrated under reduced pressure
5. temperatureThe residue was cooled to −78° C.
6. additionhydrazine monohydrate (17.3 mL) was added
7. temperaturethe mixture was warmed to room temperature
8. stirringby stirring
9. stirringThe reaction mixture was stirred at 80° C. for 10 min
10. temperaturecooled to room temperature
11. additionPotassium hydroxide (12.0 g) was added to the reaction mixture
12. stirringthe mixture was stirred at 100° C. for 16 hr
13. additionWater was added to the reaction mixture
14. washthe aqueous layer was washed with diethyl ether
15. extractionthe mixture was extracted with ethyl acetate
16. washThe extract was washed with saturated brine
17. dry with materialdried over anhydrous magnesium sulfate
18. concentrationconcentrated under reduced pressure
19. additionTo a solution of the residue in ethanol (500 mL) was added thionyl chloride (6.23 mL) under ice-
20. temperaturecooling
21. temperaturethe mixture was warmed to room temperature
22. stirringstirred at room temperature for 16 hr
23. concentrationThe reaction mixture was concentrated under reduced pressure
24. customthe residue was recrystallized from hexane-ether