Reacción #49054
ord-0c9e9cc262c14155b3bb91fc9f00a47a
Ecuación de reacción
Reactantes
Reactivos
Disolventes
Condiciones de reacción
Tratamiento posterior
- 1Extracciónthe reaction mixture was extracted with ethyl acetate
- 2LavadoThe organic layer was washed sequentially with water and saturated brine
- 3Secadodried over anhydrous sodium sulfate
- 4Concentraciónconcentrated under reduced pressure
Procedimiento
Aqueous osmium tetroxide (4%, 0.1 mL) and sodium metaperiodate (12 mg, 0.056 mmol) were added to a solution of 5-(acryloylamino-methyl)-N-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide (7.3 mg, 0.011 mmol) obtained in Step B in tetrahydrofuran (4 mL) and water (1 mL). The mixture was stirred for 3 hours. After the disappearance of the starting material was confirmed by LC/MS, the reaction mixture was extracted with ethyl acetate. The organic layer was washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give N-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-[(2-oxo-acetylamino)-methyl]-benzamide. Subsequently, this was dissolved in methanol (2.0 mL). Sodium borohydride (3 mg, 0.079 mmol) was added to this solution at room temperature, and the mixture was stirred for 1 hour. 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 by silica gel flash chromatography (Mega Bond Elut, Varian, 60% ethyl acetate/hexane as an eluent) to give 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, 60% in 2 steps) as a pale yellow solid.