反应详情

N-[2-(t-butyldimethylsilanyloxy)-ethoxy]-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-5-(hydroxyiminomethyl)-benzamide (a mixture of two geometric or atropisomers ) (5.0 mg, 46%) prepared in Process C was dissolved in THF (1 ml), tetrabutylammonium fluoride (1 M solution in THF, 30 μl, 30 μmol) was added thereto, and the mixture was stirred at room temperature for five hours. Water (8 ml) was added to the reaction solution, which was extracted with ethyl acetate (8 ml×3). The organic layers were combined, washed with 0.1 N hydrochloric acid (8 ml) and saturated brine (8 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified with preparative thin layer chromatography (Silicagel 60 F254, 0.5 mm thickness, Merck & Co., Inc., CH2Cl2/MeOH (10:1)) to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(hydroxyiminomethyl)-benzamide (Compound 3) (3.9 mg, 96%) as a white solid.

1. customatropisomers ) (5.0 mg, 46%) prepared in Process C
2. extractionwas extracted with ethyl acetate (8 ml×3)
3. washwashed with 0.1 N hydrochloric acid (8 ml) and saturated brine (8 ml)
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified with preparative thin layer chromatography (Silicagel 60 F254, 0.5 mm thickness, Merck & Co., Inc., CH2Cl2/MeOH (10:1))