Reacción #49030

Ecuación de reacción

sodium bicarbonate

(E)-5-[(2-acetylamino-ethoxyimino)-methyl]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide

(E)-5-[(2-Acetylamino-ethoxyimino)-methyl]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide

dichloromethane

dichloroacetic acid

→

5-[(2-acetylamino-ethoxyamino)-methyl]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide

Rendimiento 76.1%

Disolventes

water

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGAfter stirring for 3 hours
2. 2
   Extracciónwas then extracted with methylene chloride (15 ml and 2×8 ml)
3. 3
   LavadoThe combined organic layers were washed with aqueous sodium bicarbonate (8 ml) and saturated aqueous sodium chloride (8 ml)
4. 4
   Secadodried over anhydrous sodium sulfate
5. 5
   Concentraciónconcentrated under reduced pressure
6. 6
   OtroThe residue was purified by silica gel column chromatography (methylene chloride/methanol (10:1))

Procedimiento

To (E)-5-[(2-acetylamino-ethoxyimino)-methyl]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide (57.6 mg, 99.3 μmol) obtained in Step D was added dichloromethane (2.5 ml). The mixture was stirred at room temperature, and borane-pyridine complex (80 μl, 0.79 mmol) and dichloroacetic acid (67 μl, 0.80 mmol) were added thereto. After stirring for 3 hours, water (10 ml) and saturated aqueous sodium bicarbonate (2 ml) were added to the reaction mixture, which was then extracted with methylene chloride (15 ml and 2×8 ml). The combined organic layers were washed with aqueous sodium bicarbonate (8 ml) and saturated aqueous sodium chloride (8 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride/methanol (10:1)) to give 5-[(2-acetylamino-ethoxyamino)-methyl]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide (Compound C-7, 44.0 mg, 76%).

Fuente