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Example 14 Preparation of 4-bromo-2,5-difluoroaniline: To a stirred mixture of 100 g of 2,5-difluoroaniline and 1150 mL of acetic acid (AcOH) was slowly added 40.2 mL of bromine (Br2) in 350 mL of acetic acid (AcOH) over a period of 1.3 h. The reaction temperature was maintained at a temperature of between 15 °C and 20 °C. The reaction was carried out over a period of 2.3 hours. Upon completion of the reaction, the resulting pink suspension was continued to be stirred for 30 minutes, followed by vacuum evaporation to remove the solvent. The residue was alkalized with 50% sodium hydroxide (NaOH) solution (ice was added during the process to maintain the temperature below 35°C). The free base was extracted with 1 L of dichloromethane (CH2Cl2), and the extract was washed with 2 x 100 mL of water (H2O), dried over anhydrous sodium sulfate (Na2SO4), and finally the solvent was evaporated under vacuum to afford 157 g (97.5% yield) of the target product 4-bromo-2,5-difluoroaniline, with melting points ranging from 73°C to 75°C. Mass spectrometry analysis showed the M+1 ion peaks at 208 and 210.