Synthesis
The general procedure for the synthesis of 2-amino-4-methylbenzoic acid from 2-bromo-5-methylaniline was as follows: 2-bromo-5-methylaniline (10.0 g, 53.7 mmol) was dissolved in anhydrous ethyl ether (500 mL) under protection of nitrogen atmosphere, cooled to -78 °C and stirred. Tert-butyl lithium (127 mL, 1.7 M solution, 214.8 mmol) in pentane was added slowly over 15 minutes, keeping the reaction temperature from exceeding -65 °C. After addition, stirring was continued at -78°C for 1.5 hours. Subsequently, the reaction was quenched with excess crushed dry ice (solid CO2). After complete evaporation of the dry ice, water was added to the reaction mixture and the organic layer was separated and discarded. The aqueous layer was acidified with 1N hydrochloric acid and then extracted with two parts of ethyl acetate. The organic extracts were combined, dried with anhydrous magnesium sulfate, filtered and concentrated to give the target product 2-amino-4-methylbenzoic acid (4.8 g, 59% yield) as a tan crystalline solid. Mass spectrum (chemical ionization): 152 (M+H).
