1310350-99-2

1310351-06-4

1310350-99-2

c) Synthesis of 4-chloro-1-(difluoromethyl)-1H-pyrazole-3-carboxylic acid: Methyl 4-chloro-1-(difluoromethyl)-1H-pyrazole-3-carboxylate (540 mg, 2.6 mmol) was dissolved in tetrahydrofuran (18 mL), and a mixture of aqueous and methanol (1:1, 12 mL) of lithium hydroxide (135 mg, 5.6 mmol) was slowly added at room temperature. After 1 h of reaction, most of the solvent was removed by concentration under reduced pressure. The residue was dissolved in water (10 mL) and acidified with 2 M hydrochloric acid to pH ≈ 2. Subsequent extraction with ethyl acetate, drying of the organic phase with anhydrous sodium sulfate, and concentration under reduced pressure afforded a white solid crude product (555 mg). The crude product was ground with pentane (10 mL), the solid was collected by filtration and washed with pentane and dried under reduced pressure to give 4-chloro-1-(difluoromethyl)-1H-pyrazole-3-carboxylic acid (477 mg, 95% yield). Mass spectrum (ISP): m/z = 195.0 [M-H]?