438450-38-5

124-38-9

438450-39-6

Step B: Preparation of 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid. A solution of 3-chloro-2-[3-(trifluoromethyl)-1H-pyrazol-1-yl]pyridine (i.e., the product of Step A, 105.0 g, 425 mmol) in anhydrous tetrahydrofuran (700 mL) was transferred through a cannula into the reactor at -75 °C. Subsequently, an anhydrous tetrahydrofuran (300 mL) solution of lithium diisopropylammonium (425 mmol) was slowly added at -30 °C. The resulting dark red solution was stirred for 15 minutes, and then carbon dioxide gas was passed at -63 °C until the color of the solution changed to light yellow and the exothermic phenomenon stopped. Stirring of the reaction mixture was continued for 20 minutes, after which the reaction was quenched with water (20 mL). The solvent was removed by distillation under reduced pressure and the residue was partitioned between ether and 0.5 N aqueous sodium hydroxide. The aqueous phase was washed three times (3×) with ether, filtered through a Celite diatomaceous earth filter aid to remove insoluble impurities, and subsequently adjusted the pH with acid to about 4, at which point an orange colored oil formed. The pH was adjusted to 2.5-3 by vigorous stirring of the aqueous phase and further addition of acid to induce coagulation of the orange oily material into a granular solid. The solid was collected by filtration, washed sequentially with water and 1N hydrochloric acid, and finally dried under vacuum at 50 °C to afford the title product 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid as an off-white solid (130 g). The product prepared by another similar procedure had a melting point of 175-176°C. 1H NMR (DMSO-d6) δ: 7.61 (s, 1H), 7.76 (dd, 1H), 8.31 (d, 1H), 8.60 (d, 1H).