2-BROMO-4-FLUORO-6-METHYLANILINE synthesis

Yield: 92%

Reaction Conditions:

with N-Bromosuccinimide in N,N-dimethyl-formamide at -10 - 20; for 16 h;

Steps:

1 Step 1:
To a solution of 4-fluoro-2-methyl-phenylamine (30 g, 0.239 mol) in DMF (450 ml) was added NBS (44.81 g, 0.251 mol) portionwise at -10 °C. The resulting reaction mixture was stirred at room temperature for 16 h. After completion of the reaction (monitored by LCMS), the reaction mixture was diluted with water (1000 ml) and extracted with ethyl acetate (2 x 500 ml). The combined organic layers were washed with water (2 x 500 ml) and brine (250 ml), dried over anhydrous Na₂SO₄and concentrated to afford the crude compound, which was purified by column chromatography (100-200 mesh silica gel; 10% ethyl acetate/hexane) to afford 2-bromo-4-fluoro-6-methyl- phenylamine (45 g, 92%) as a white solid

References:

GRÜNENTHAL GMBH WO2021/144440, 2021, A1 Location in patent:Page/Page column 29-30