反应详情

温度

-78 °C

To a chilled (−78 C.) solution of 40 mg (0.30 mmol) of 2-methylindole in 3 mL of diethyl ether was added 0.56 mL (0.91 mmol) of a 1.6 M solution of n-BuLi in hexanes. The resulting orange solution was stirred for 5 min and treated with 0.60 mL (0.60 mmol) of a solution of 1 M solution of KOt-Bu in THF. The reaction was slowly warmed until a bright yellow precipitate formed. After 5 min, the reaction mixture was cooled to −78° C. and treated with 138 mg (0.362 mmol) of a solution of 2-methyl-propane-2-sulfinic acid [3-(5-fluoro-2-methoxy-phenyl)-3-methyl-1-trifluoromethyl-but-(Z)-ylidene]-amide in 0.5 mL of diethyl ether. Next, the mixture was warmed to room temperature, quenched with aqueous ammonium chloride and extracted with EtOAc (3×). The combined organic layers were dried over (MgSO4), filtered and concentrated. The residue was dissolved in 2 mL of methanol, 3 drops of concentrated HCl were added and the reaction warmed at 75° C. in a sealed tube. After 1 h, the reaction was cooled to room temperature, concentrated in vacuo, neutralized with aqueous sodium bicarbonate and extracted with EtOAc (3×). The combined organic layers were dried (MgSO4), filtered and concentrated to leave an oil. The residue was purified by preparative thin layer chromatography eluting with toluene to afford an oil that had to be further purified by preparative thin layer chromatography eluting with hexanes-EtOAc (9:1) to afford 40 mg (33%) of the title compound.

1. temperatureThe reaction was slowly warmed until a bright yellow precipitate
2. customformed
3. waitAfter 5 min
4. temperatureNext, the mixture was warmed to room temperature
5. customquenched with aqueous ammonium chloride
6. extractionextracted with EtOAc (3×)
7. dry with materialThe combined organic layers were dried over (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated
10. dissolutionThe residue was dissolved in 2 mL of methanol
11. addition3 drops of concentrated HCl were added
12. temperaturethe reaction warmed at 75° C. in a sealed tube
13. waitAfter 1 h
14. temperaturethe reaction was cooled to room temperature
15. concentrationconcentrated in vacuo
16. extractionextracted with EtOAc (3×)
17. dry with materialThe combined organic layers were dried (MgSO4)
18. filtrationfiltered
19. concentrationconcentrated
20. customto leave an oil
21. customThe residue was purified by preparative thin layer chromatography
22. washeluting with toluene
23. customto afford an oil that
24. customto be further purified by preparative thin layer chromatography
25. washeluting with hexanes-EtOAc (9:1)