反应详情

Tert-butyl-2-(1-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzoyl)-3-hydroxyazetidin-3-yl)cyclohexylcarbamate was dissolved in a mixture of methanol (4 mL) and hydrogen chloride (4 M in dioxane) (3 mL). The solution was heated to reflux then cooled to room temperature and stirred for 16 hours. The reaction mixture was concentrated and purified by reverse phase HPLC. The purified fractions were evaporated to dryness and partitioned between ethyl acetate and aqueous sodium bicarbonate. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to afford an oil. The residue was taken up in methanol (2 mL) and was added hydrogen chloride (4M in dioxane) (700 μL) and evaporated to dryness to afford the title compound 3-(2-aminocyclohexyl)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol hydrochloride (44.7 mg, 12%).

1. temperatureThe solution was heated
2. temperatureto reflux
3. concentrationThe reaction mixture was concentrated
4. custompurified by reverse phase HPLC
5. customThe purified fractions were evaporated to dryness
6. custompartitioned between ethyl acetate and aqueous sodium bicarbonate
7. dry with materialThe organic layer was dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customto afford an oil
11. customevaporated to dryness