Synthesis
The general procedure for the synthesis of methyl 3-amino-5-bromo-2-hydroxybenzoate from methyl 5-bromo-2-hydroxy-3-nitrobenzoate (138.02 g, 0.5 mol) and methanol (1000 mL) was as follows: methyl 5-bromo-2-hydroxy-3-nitrobenzoate was mixed with methanol, followed by a one-time addition of activated iron powder (112 g, 2 mol). The reaction mixture was heated to a slightly refluxed state, saturated ammonium chloride solution (80 g, 1.5 mol) was slowly added dropwise and the reflux reaction was maintained for 3 hours. The progress of the reaction was monitored by thin layer chromatography (TLC) and after confirming the completion of the reaction, the reaction system was cooled to room temperature. Diatomaceous earth (200 g) was added to the cooled reaction mixture and filtration was carried out to obtain a black filtrate. The solid residue was washed well with hot methanol until no product was detected in the wash solution and the black solid was discarded. All the filtrates were combined and the solvent was removed by evaporation under reduced pressure. The crude product was purified by rapid chromatography on an 80-100 mesh silica gel column to afford methyl 3-amino-5-bromo-2-hydroxybenzoate (96-85 g) in 78% yield.
