4-Amido-2-(diethylaminomethyl)phenol (14, 50 g, 0.212 mol, 1.0 equiv.) was added to a flask charged with 32% HCl (110 mL, 0.966 mol). The mixture was stirred for 15 min. at room temperature followed by reflux at 85 °C for 4 h. H2O (200 mL) was added to the flask, the heating was turned off and the temperature allowed to cool to 50 °C. The pH of the mixture was adjusted to 4 using 25% aq. NaOH solution. 4,7-DCQ (5, 42 g, 0.212 mol, 1.0 equiv.) was added to the mixture. The mixture was then refluxed at 85 °C for 3 h followed by stirring the mixture at 5 °C for 2 h. The yellow product was collected by vacuum filtration and washed with water (2x 50 mL). The crude amodiaquine was kept under vacuum for 30 minutes after which it was refluxed in a 300 mL solution of EtOH/HCl (5:1 equiv.) for 2 h at 80 °C. The yellow product was then allowed to precipitate at 5-10 °C for 2 h at which time it was filtered in vacuo, washed with a 100 mL cold solution of EtOH/HCl (5:1 equiv.) and air-dried overnight. The product was then refluxed in water (2.5 mL/g) at 95 °C for 2 h followed by precipitation overnight at room temperature under stirring. The reaction mixture was cooled to 0-5 °C for 2 h. The product was filtered in vacuo, washed with cold water (2x 50 mL) and airdried overnight before drying in the oven at 40 °C to obtain 3 (88.5 g, 0.190 mol, 90%) as a yellow solid. HPLC (C18) PHPLC 100%, tR 6.2 min. mp = 159-166 °C (lit. = 160°C). Water content = 8% (USP standard = 7.0% -9.0%).