Reacción #49035

Ecuación de reacción

methanesulfonylethanol

triethylsilane

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

→

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

Rendimiento 21.0%

Disolventes

methylene chloride

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 2% aqueous EDTA, 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 preparative TLC (No

Procedimiento

To a suspension of 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-formyl-N-(2-hydroxy-ethoxy)-benzamide (52 mg, 0.108 mmol) obtained in Step F of Example 1 in methylene chloride (anhydrous, 5 mL) were added copper trifluoromethanesulfonate (20 mg, 0.005 mmol), methanesulfonylethanol (200 μL), and triethylsilane (500 μL, 3.13 mmol) under a nitrogen atmosphere, and the mixture was stirred thoroughly for a whole day and night. After completion of the reaction, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed sequentially with 2% aqueous EDTA, water, and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resultant residue was purified by preparative TLC (No. 5744, Merck, 5% methanol/methylene chloride as a developing solvent) to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(2-methanesulfonyl-ethoxymethyl)-benzamide (13.3 mg, 21%) as a white solid.

Fuente