General procedure for the synthesis of 2-bromo-5-fluoro-4-methylaniline from 3-fluoro-4-methylaniline:
Step A- Synthesis of compound 28B:
Compound 28A (3-fluoro-4-methylaniline, 6.00 g, 47.9 mmol) and anhydrous potassium carbonate (6.70 g, 48.5 mmol) were dissolved in anhydrous dichloromethane (130 mL), and the mixture was cooled to -15 °C in a salt-ice bath. Subsequently, a solution of bromine (7.70 g, 48.2 mmol) in anhydrous dichloromethane (80 mL) was slowly added dropwise. After the dropwise addition was completed, the reaction temperature was maintained at -15 °C and stirring was continued for 1 hour. Upon completion of the reaction, the reaction was quenched by the addition of ice water (100 mL) to the reaction mixture and the aqueous layer was extracted with dichloromethane (2 x 100 mL). The organic layers were combined, dried with anhydrous magnesium sulfate and concentrated under reduced pressure to afford the crude product compound 28B (2-bromo-5-fluoro-4-methylaniline, 11.0 g, quantitative yield), which could be used in subsequent steps without further purification.
