5-Fluoro-2-nitro-4-trifluoromethyl-benzoic acid methyl ester → 1-(5-methoxycarbonyl-4-nitro-2-trifluoromethyl-phenyl)-1H-imidazole-4-carboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 8.00 g (29.95 mmol) of 5-fluoro-2-nitro-4-trifluoromethyl-benzoic acid methyl ester in 40 ml dry tetrahydrofuran, 5.40 g (42.00 mmol) of 1H-imidazole-4-carboxylic acid methyl ester are added. The reaction mixture is stirred at 70° C. for 48 hours (after 16 hours addition of 0.3 equivalents of 1H-imidazole-4-carboxylic acid methyl ester). Subsequently the solvent is evaporated and the light brown residue is extracted with dichloromethane. The combined organic extracts are dried, the solvent evaporated to give light purple crystals. The crude product is purified by flash-master chromatography (dichloromethane/methanol 100-90/0-10 gradient) to yield 1-(5-methoxycarbonyl-4-nitro-2-trifluoromethyl-phenyl)-1H-imidazole-4-carboxylic acid methyl ester. 1H-NMR; DMSO-d6 (400 MHz, ppm): 8.71 (s, 1H , aromatic); 8.31 (s, 1H , aromatic); 8.27 (s, 1H, imdazole); 8.09 (s, 1H, imdazole); 3.92 (s, 3H Ar-COOCH3); 3.80 (s, 3H, COOCH3); LC-MS: 374 [M+H]+; Agilent LC/MSD 1100 Series; LC-MS method: Column: SunFireC18, 4.6*50 mm, 3.5 μm; positive MS; water/acetonitril 95:5 to 5:95 in 5 min, flow: 1.5 ml/min.

Provenance & Evidence