A 22-liter three-necked round-bottom flask (RBF) was assembled with an electric heating jacket, thermocouple probe, overhead mechanical stirrer, water-cooled condenser, nitrogen bubbler, and charging funnel. 4-Amino-3-methoxybenzoic acid (1.0 kg, 5.98 mol, 1.0 eq.) and ethanol (10.0 l, 10 v/v) were added to the flask to form a stir-able slurry. Sulfuric acid (1.17 kg, 0.64 L, 12.0 mol, 2.0 eq.) was slowly added for 1 hour without external cooling. The slurry initially thickened, then dispersed and eventually dissolved completely to form a dark solution. Exotherm during spiking raised the temperature to 45 °C; additional heat was then applied to reflux the solution and it was kept refluxing overnight. Analysis by HPLC sampling showed 5% of the starting benzoic acid remaining. The condenser was switched to distillation mode and 2.5 liters of solvent was distilled. The reaction mixture was cooled to 6 °C in an ice bath and the pH was adjusted to 12 by slow addition of aqueous sodium hydroxide (50 wt%, 1.03 kg, 681 mL, 12.9 mol, 2.15 eq.), controlling the temperature to be below 20 °C. After stirring for 30 minutes, an additional amount of water (4.0 liters) was added and stirring was continued for 30 minutes at about 10°C. The solid product was collected by filtration, washed thoroughly with water (4.0 liters) and subsequently dried under vacuum at 65 °C overnight. Ethyl 4-amino-3-methoxybenzoate 1.04 kg (89.1% yield) was obtained as a light brown solid. Melting point: 83-87 °C (DSC measurement); 1H NMR (300 MHz, CDCl3) δ 7.56 (1H, dd, J = 7.9,1.5 Hz), 7.47 (1H, d, J = 1.5 Hz), 6.66 (1H, d, J = 7.9 Hz), 4.33 (2H, t, J = 7.2 Hz), 4.27 (1H, br s) , 3.90 (3H, s), 1.37 (3H, t, J = 7.2 Hz).
