1-methyl-1H-pyrazole-3-carboxylic acid → 4-fluoro-1-methyl-1H-pyrazole-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a 200 mL round-bottomed flask equipped with a reflux condenser and stir bar, were added 1-methyl-1H-pyrazole-3-carboxylic acid (1.5 g, 11.9 mmol), dry acetonitrile (60 mL), and Selectfluor® (12.6 g, 35.7 mmol). The reaction vessel was heated to 80° Celsius for 32 h. Additional Selectfluor® (8.5 g, 24.0 mmol) was added to the reaction mixture and it was stirred at 80° Celsius for 5 days. The reaction mixture was cooled to RT and the solids were removed by filtration. The filtrate was concentrated to dryness and subjected to FCC to yield crude title compound (330 mg, 13% yield). The impure material was then recrystallized from hot methanol to give the title compound as long yellow crystals. Additional title compound could be obtained from the mother liquor by filtration of the solid that forms upon concentration (11.53 g total combined yield, 70%). The crystallized title compound contained minor impurities, but was used in subsequent steps without further purification. Analytically pure title compound can be obtained by subjecting it to HPLC purification. MS (ESI): mass calcd. for C5H5FN2O2 144.03, m/z found 145.0 [M+H]+ (low intensity).

Provenance & Evidence