Selectfluor → 4-Fluoro-5-(2-methoxy-5-nitro-phenyl)-1-methyl-1H-pyrazole

HRID 540546Notes

Reaction equation

HRID 540546 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:4]=1[C:12]1[N:16]([CH3:17])[N:15]=[CH:14][CH:13]=1.[B-](F)(F)(F)[F:19].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1>C(#N)C>[F:19][C:13]1[CH:14]=[N:15][N:16]([CH3:17])[C:12]=1[C:4]1[CH:5]=[C:6]([N+:9]([O-:11])=[O:10])[CH:7]=[CH:8][C:3]=1[O:2][CH3:1]

Participants

5

Reactant 2

HCID 2724933SelectfluorHCID 231395315-(2-Methoxy-5-nitrophenyl)-1-methyl-1H-pyrazole

Product 1

HCID 231394304-Fluoro-5-(2-methoxy-5-nitro-phenyl)-1-methyl-1H-pyrazoleYield 33.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 178435178HCID 178435178, compoundSolvent

Conditions

Temperature
80 °C

Procedure

5-(2-Methoxy-5-nitro-phenyl)-1-methyl-1H-pyrazole (300.0 mg, 1.29 mmol) was dissolved in ACN (15 ml) in a polypropylene 20 mL scintillation vial. To this solution, Selectfluor (913.9 mg, 2.58 mmol) was added and the mixture was degassed with argon and heated to 80° C. for 6 hours. The solvent was removed under reduced pressure and the residue was dissolved in 50 mL EtOAc and 30 mL 3N HCl. The organic layer was separated and the aqueous layer was extracted with EtOAc (2×50 ml). The organic layers were combined, dried over Na2SO4, filtered, and the solvent removed under reduced pressure. The residue was then purified by flash chromatography (Biotage SiO2, Hexanes (0.01% TEA)/EtOAc gradient elution) to afford 108 mg (33%) of 4-fluoro-5-(2-methoxy-5-nitro-phenyl)-1-methyl-1H-pyrazole as a white solid. LCMS m/z (%)=252 (M+H, 100). 1H NMR (400 MHz, CDCl3) δ: 8.39 (d, J=9.2 Hz, 1H), 8.22 (s, 1H), 7.44 (d, JH,F=4.4 Hz, 1H), 7.12 (d, J=9.2 Hz, 1H) 3.98 (s, 3H), 3.77 (s, 3H). 19F NMR (376 MHz, CDCl3) δ: −175.50 (d, JH,F=5.3 Hz, 1F).

Workup

  1. customthe mixture was degassed with argon
  2. customThe solvent was removed under reduced pressure
  3. dissolutionthe residue was dissolved in 50 mL EtOAc
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with EtOAc (2×50 ml)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customthe solvent removed under reduced pressure
  9. customThe residue was then purified by flash chromatography (Biotage SiO2, Hexanes (0.01% TEA)/EtOAc gradient elution)

Sources & evidence

ORD record
ord-010edfb0e80c44998c7e00215cbdb916
Source dataset
uspto-grants-2014_10
Patent number
US08871797B2

Reaction notes

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