Nitric Acid → 2-Fluoro-5-methoxyaniline

Participants

Reaction Conditions

Reaction Steps

To a stirred mixture of 2,6-dibromo-4-fluoroanisole (52.5 g, 0.185 mol) in 98% sulfuric acid (152 mL) at 15° C. was added, dropwise over 0.5 h, a solution of nitric acid (9.2 mL) and sulfuric acid (152 mL) with external ice-bath cooling. The mixture was stirred at 20° C. over 4 h, then was poured into ice water (1 kg) and extracted with dichloromethane (3×150 mL). The combined extracts were dried (Na2SO4) and evaporated in vacuo to give a brown oil. Chromatography on silica with 1-50% ether in hexane gradient elution gave an off-white solid, a solution of which in ethanol (250 mL) was hydrogenated at 20° C. and 4 bar over 10% palladium on carbon (3.5 g) for 18 h. Catalyst was removed by filtration and the filtrate was evaporated in vacuo to give a residue which was partitioned between saturated aqueous NaHCO3 (300 mL) and dichloromethane (3×100 mL). The combined organic extracts were dried (Na2SO4) and evaporated in vacuo to give an oil. Chromatography on silica with 20-50% ether in hexane gradient elution gave the title compound (15.3 g, 59%) as an oil.

Provenance & Evidence