Methyl iodide → 4-Bromo-3-methoxy-N-methyl-2-nitroaniline

Participants

Reaction Conditions

Reaction Steps

A solution of N-(4-bromo-3-fluoro-2-nitrophenyl)-2,2,2-trifluoroacetamide (1.27 g, 3.84 mmol) in N,N-dimethylformamide (43.4 mL) was treated with cesium carbonate (2.50 g, 7.67 mmol) followed by the addition of methyl iodide (1.19 mL, 19.2 mmol). The reaction mixture was stirred at 20° C. for 1 h, then warmed to 50° C. and stirred at that temperature for 16 h, after which time additional methyl iodide (0.5 eq) was added to the reaction mixture and the reaction mixture was heated at 50° C. for 4 h. The reaction mixture was diluted with ethyl acetate and water. Layers were separated and the organic layer was washed with water (3×) and brine, dried with magnesium sulfate, filtered, and concentrated in vacuo to give the crude methylated amide which was used without further purification. The crude intermediate methylated amide was dissolved in methanol (43.4 mL) and water (8.68 mL, 482 mmol), treated with potassium carbonate (2.65 g, 19.2 mmol), and the resultant mixture was stirred at 60° C. for 15 h, after which time the reaction mixture was concentrated to remove most of the methanol and the aqueous residue was extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried with magnesium sulfate, filtered, and concentrated to give the desired product (906 mg, 90%) as a yellow solid. LCMS calculated for C8H10BrN2O3 (M+H)+: m/z=261.0, 263.0. found: 260.9, 262.8.

Provenance & Evidence