Methanol → Methyl 4-(allylamino)-5-amino-3-fluoro-2-(2-fluoro-4-iodophenylamino)benzoate

Participants

Reaction Steps

A stirred suspension of 4-allylamino-3-fluoro-2-(2-fluoro-4-iodo-phenylamino)-5-nitro-benzoic acid methyl ester (125.0 g, 0.25 mol), ammonium chloride (300.0 g, 8.58 mol) in 1:1 v/v mixture of methanol (4.0 lit) and dioxane (4.0 lit) was heated until it became a clear solution and was added iron powder (150.0 g, 2.68 mol) under a positive stream of nitrogen gas. The reaction mixture was refluxed for 16 h (completion of reaction is confirmed by TLC-EtOAc:Hexane/3:5) and poured onto a mixture of 10 kg of crushed ice and 6.5 L of saturated sodium bicarbonate. To the mixture was added 1 kg of Celite®, stirred and the thick suspension was filtered through a Celitetbed. The Celite® bed was rinsed with water, then with ethyl acetate and ethyl acetate layer was separated. The aqueous layer was extracted with ethyl acetate (3 L) and the combined organic extracts are washed with water (3 L), brine (2 L), dried over anhydrous Na2SO4, filtered and evaporated under vacuum to give the title compound as oil (light brown color), which was used in the next step without further purification. Yield: 110 (93.55%)

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