Reacción #49012

Ecuación de reacción

3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-formyl-N-(2-hydroxy-ethoxy)-benzamide

O,N-dimethyl-hydroxylamine hydrochloride

sodium cyanoborohydride

→

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

Rendimiento 17.0%

Disolventes

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroAfter completion of the reaction
2. 2
   Extracciónthe reaction mixture was extracted with ethyl acetate
3. 3
   Lavadothe organic layer was washed sequentially with water and saturated brine
4. 4
   Secadodried over anhydrous sodium sulfate
5. 5
   Concentraciónconcentrated under reduced pressure
6. 6
   OtroThe resultant residue was purified by silica gel flash chromatography (Mega Bond Elut, Varian, 5% methanol/methylene chloride as an eluent)

Procedimiento

To a solution of 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-formyl-N-(2-hydroxy-ethoxy)-benzamide (56.2 mg, 0.117 mmol) in tetrahydrofuran (anhydrous) were added O,N-dimethyl-hydroxylamine hydrochloride (commercially available, 34 mg, 0.351 mmol) and sodium cyanoborohydride (34 mg, 0.541 mmol) under nitrogen atmosphere, and the mixture was stirred at room temperature for 3 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 concentrated under reduced pressure. The resultant residue was purified by silica gel flash chromatography (Mega Bond Elut, Varian, 5% methanol/methylene chloride as an eluent) to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(methoxy-methyl-amino)-methyl]-benzamide (9.72 mg, 17%) as a white solid.

Fuente