反应详情

To a solution of 5-[1,3]dioxolan-2-yl-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide (21.69 g) obtained in Step G in anhydrous THF (100 ml) were added sodium borohydride (4.21 g, 111.4 mmol) and trifluoroacetic acid (5.08 ml, 66.8 mmol) with ice-cooling, and the mixture was stirred at room temperature overnight. The reaction mixture was poured into saturated aqueous sodium bicarbonate, and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (SiO2 600 g, 100% AcOEt to AcOEt/MeOH (50:1 to 20:1)) to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(2-hydroxy-ethoxymethyl)-benzamide (13.9 g, 80%) as a white powder.

1. temperaturecooling
2. extractionextracted with ethyl acetate
3. washThe organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine
4. dry with materialdried over magnesium sulfate
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by silica gel column chromatography (SiO2 600 g, 100% AcOEt to AcOEt/MeOH (50:1 to 20:1))