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

Temperature

80 °C

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).

1. customTo a 200 mL round-bottomed flask equipped with a reflux condenser
2. stirringwas stirred at 80° Celsius for 5 days
3. temperatureThe reaction mixture was cooled to RT
4. customthe solids were removed by filtration
5. concentrationThe filtrate was concentrated to dryness
6. customto yield crude title compound (330 mg, 13% yield)
7. customThe impure material was then recrystallized from hot methanol

ORD record

ord-98f0f8e012e9438dbac11f3e317213ec

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952177B2