Nitric Acid → 3-Fluoro-4-methoxyaniline

Participants

Reaction Steps

To a cold (15°), stirred solution of 12.8 g (0.0699 mol) of 4-acetamido-2-fluoroanisole in 55 mL of acetic acid and 27 mL of acetic anhydride was added, dropwise, 6.5 g (0.072 mol) of 70% nitric acid (sp. gr. 1.424) at such a rate that the temperature of the reaction mixture did not exceed 16°. The solution was stirred for 1.5 hours at room temperature then poured into 400 mL of ice-water. The aqueous suspension was extracted with methylene chloride (1×300 mL; 1×200 mL), then the combined extracts were concentrated in vacuo to a solid (13 g). The material was chromatographed on a column of silica gel (300 g) using benzene as the eluent. The fractions containing the required product were combined then concentrated in vacuo. The solid residue was dissolved in methylene chloride (400 mL) and the solution was washed with water, dried over anhydrous magnesium sulfate, then concentrated in vacuo; yield, 10.0 g (62.9%). The material was suitable for further transformation. Additional material (169 g; 44.6%) was obtained from 110 g (0.779 mol) of 4-amino-2-fluoroanisole without isolating the intermediate 4-acetamido-2-fluoroanisole (3).

Provenance & Evidence