反应详情

Tetra-n-butylammonium fluoride (1 mol/L solution in tetrahydrofuran, 0.5 mL, 0.500 mmol) was added to a solution of N-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-[(2-hydroxy-acetylamino)-methyl]-benzamide (4.34 mg, 0.00665 mmol) obtained in Step C in tetrahydrofuran (anhydrous, 1 mL) at room temperature. The mixture was stirred for 1.5 hours. After completion of the reaction, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and evaporated under reduced pressure. The resultant crude product was purified sequentially with silica gel flash chromatography (Mega Bond Elut, Varian, 5% methanol/methylene chloride as an eluent) and preparative TLC (No. 5715, Merck, 7% methanol/methylene chloride as a developing solvent) to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-[(2-hydroxy-acetylamino)-methyl]-N-(2-hydroxy-ethoxy)-benzamide (Compound E-5, 1.4 mg, 39%) as a white solid.

1. customAfter completion of the reaction
2. extractionthe reaction mixture was extracted with ethyl acetate
3. washthe organic layer was washed sequentially with water and saturated brine
4. dry with materialdried over anhydrous sodium sulfate
5. customevaporated under reduced pressure
6. customThe resultant crude product was purified sequentially with silica gel flash chromatography (Mega Bond Elut, Varian, 5% methanol/methylene chloride as an eluent) and preparative TLC (No