328547-11-1

67-56-1

954571-39-2

328547-11-1

Step 1. 5-Fluoro-7-nitroindoline-2,3-dione (1.5 g, 7.4 mmol) was suspended in aqueous NaOH (5N, 14.0 mL) followed by addition of aqueous H2O2 (2.0 mL). The reaction mixture was stirred at room temperature for 5 h and then acidified with 2N HCl to pH=4.0. The resulting precipitate was filtered and dried in a vacuum oven to give a crude product which was used directly in the next step of the reaction. Step 2. The crude product obtained from Step 1 was dissolved in methanol (15.0 mL) and p-toluenesulfonic acid hydrate (1.33 g, 7.0 mmol) was added. The reaction mixture was refluxed for 36 hours. After cooling to room temperature, the reaction mixture was concentrated in vacuum to obtain the crude product. The crude product was purified by silica gel column chromatography with petroleum ether/ethyl acetate (8:1, v/v) as eluent to give the yellow solid product methyl 2-amino-5-fluoro-3-nitrobenzoate (500 mg, 32% overall yield in two steps).