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

Participants

Reaction Steps

To a solution of (E)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(2-hydroxy-ethoxyimino)-methyl]-benzamide (3.62 g, 6.70 mmol) obtained in Step B in methanol (100 ml) were added portionwise trifluoroacetic acid (6.5 ml) and sodium cyanoborohydride (3.78 g, 60.2 mmol) over 2 days while monitoring the progression of the reaction by TLC. The reaction mixture was poured into water, and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (CH2Cl2/MeOH (15:1)), and the resultant crude compound was crystallized from methylene chloride to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(2-hydroxy-ethoxyamino)-methyl]-benzamide (1.66 g, 46%, as a total of first and second crystals).

Provenance & Evidence