methyl 2-amino-5-methyl-4-(trifluoromethyl)benzoate

872624-52-7

13061-96-6

872624-53-8

Step 4: Preparation of methyl 2-amino-5-methyl-4-(trifluoromethyl)benzoate To a solution of methyl 2-amino-5-iodo-4-(trifluoromethyl)benzoate (121 g, 351 mmol) in anhydrous 1,4-dioxane (2.5 L) under nitrogen protection was added sequentially cesium fluoride (184.3 g, 1.21 mol), methylboronic acid (63.7 g, 1.05 mol, 3 molar equivalents), and bis(diphenylphosphinoferrocene)palladium chloride (II ) (27.83 g, 35.1 mmol). The reaction mixture was heated and stirred at 80 °C for 3 hours. Upon completion of the reaction, which was cooled to room temperature, the reaction solution was partitioned between ethyl acetate (2.5 L) and water (2.5 L) and filtered through a Celite pad to remove the fine black suspension. The organic phase was separated and the aqueous phase was extracted with ethyl acetate (2 x 100 mL). The organic phases were combined, washed with brine (1 L) and dried over anhydrous magnesium sulfate. After filtration, it was concentrated under reduced pressure (45°C) to obtain a red oil. Purification by silica gel column chromatography with isohexane/ethyl acetate (9:1) as eluent gave methyl 2-amino-5-methyl-4-(trifluoromethyl)benzoate (75.25 g, 92% yield) as a light yellow crystalline solid.