反应详情

A solution of 0.2 g (0.47 mmol) [5-(tetrahydro-pyran-4-yl)-1,3-dihydro-isoindol-2-yl]-[2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone in 2 ml of 1,2-dichloroethane was added dropwise to 0.32 ml (4.7 mmol) chlorosulfonic acid under ice bath cooling. The mixture was stirred at room temperature for 30 minutes and then at 55° C. for 30 minutes. The mixture was cooled in an ice bath and quenched by dropwise addition of 2 ml water. The mixture was diluted with dichloromethane. The organic layer was separated and the aqueous layer was extracted twice with dichloromethane. The combined dichloromethane extracts were dried over Na2SO4, filtered and concentrated in vacuo. The obtained foam was stirred with ethylacetate. The solid was filtrated. The filtrate was washed twice with a saturated solution of NaHCO3, dried over Na2SO4, filtered and concentrated in vacuo to provide 0.12 g (51%) of the title compound as light yellow foam. MS (m/e): 517.1 [M]+.

1. temperaturecooling
2. waitat 55° C. for 30 minutes
3. temperatureThe mixture was cooled in an ice bath
4. customquenched by dropwise addition of 2 ml water
5. additionThe mixture was diluted with dichloromethane
6. customThe organic layer was separated
7. extractionthe aqueous layer was extracted twice with dichloromethane
8. dry with materialThe combined dichloromethane extracts were dried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. stirringThe obtained foam was stirred with ethylacetate
12. filtrationThe solid was filtrated
13. washThe filtrate was washed twice with a saturated solution of NaHCO3
14. dry with materialdried over Na2SO4
15. filtrationfiltered
16. concentrationconcentrated in vacuo