62257-15-2

346664-78-6

62257-15-2

The general procedure for the synthesis of 2-fluoro-5-methoxyaniline from 1,3-dibromo-5-fluoro-2-methoxy-4-nitrobenzene is as follows: 1,3-dibromo-5-fluoro-2-methoxy-4-nitrobenzene (50 g, 0.152 mol) was dissolved in anhydrous ethanol (1.5 L) under the protection of nitrogen and catalyst was added. The reaction mixture was first evacuated under stirring and then hydrogen was passed under 3 bar pressure. Subsequently, the reaction mixture was again evacuated and hydrogen was passed to a pressure of 7 bar. The reaction was continuously stirred at 25°C for 48 hours, during which time hydrogen was periodically replenished to maintain an internal pressure of 7 bar (Note: the catalyst needs to be replaced after 24 hours). Upon completion of the reaction, the catalyst is removed by filtration through two glass microfiber pads under nitrogen protection and the filtrate is concentrated to dryness at 45°C under reduced pressure. The resulting dark orange solid was dissolved in water (500 mL) and the pH was adjusted to >12 with aqueous 1N NaOH (400 mL).The resulting brown suspension was extracted with tert-butyl methyl ether (2 x 1 L). The organic phase was washed with water (500 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure at 40 °C to give 2-fluoro-5-methoxyaniline (18.0 g, 84% yield) as a brown solid. The product was analyzed by 1H NMR [(CD3)2SO] δ 6.87 (dd, J = 11.1, 8.7 Hz, 1H), 6.33 (dd, J = 7.7, 3.2 Hz, 1H), 6.05 (dt, J = 8.7, 3.2 Hz, 1H), 5.11 (br s, 2H), 3.65 (s, OCH3, 3H); MS (ES) m/z 183 (M + CH3CN + H)+ confirmed.