The general procedure for the synthesis of 5-(3-chlorophenyl)-3-methoxypicolinonitrile as a raw material for 5-(3-chlorophenyl)-3-hydroxypyridine carboxylic acid was as follows: to a 20 L reactor equipped with a mechanical stirrer, condenser tube, thermometer and nitrogen inlet was added 5-(3-chlorophenyl)-3-methoxy-2-cyano-pyridine (440.6 g, 1.8 mol) and 37% hydrochloric acid aqueous solution (5302g). The reaction mixture was heated to 102 °C under stirring and maintained for 24 hours. Subsequently, 37% aqueous hydrochloric acid solution (2653 g) was added and stirring was continued at 104 °C for 18 hours. After completion of the reaction, the mixture was cooled to 5 °C, water (4410 g) was added and stirred at 0 °C for 16 hours. The precipitated product was separated by filtration and washed with water until the filtrate had a pH of 6 (about 8000 L of water was consumed). The filter cake was dried under reduced pressure for 2 hours. Afterwards, the filter cake was retransferred to a reactor and ground with THF (1958 g, 2201 mL) for 2 hours at room temperature. The solid product was again separated by filtration and washed with THF (778 g, 875 mL), and finally dried under reduced pressure for 48 h at 5 °C to give an off-white solid product of 385 g (89% yield). HPLC analysis showed the product purity to be 96.2%.1H NMR (DMSO-d6) data were as follows: δ 8.52 (d, 1H), 7.99 (d, 1H) 7.95 (s, 1H), 7.81 (t, 1H), 7.57 (s, 1H), 7.55 (s, 1H).
