Hydrochloric Acid → 3-(3-Fluoro-4-nitrophenyloxy)-5-methylpyrazole

HRID 644834Notes

Reaction equation

HRID 644834 reaction equation
C(=O)([O-])[O-].[K+].[K+].[F:7][C:8]1[CH:13]=[C:12](F)[CH:11]=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16].[OH:18][C:19]1[CH:23]=[C:22]([CH3:24])[NH:21][N:20]=1.Cl>CS(C)=O>[F:7][C:8]1[CH:13]=[C:12]([O:18][C:19]2[CH:23]=[C:22]([CH3:24])[NH:21][N:20]=2)[CH:11]=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 679672,4-DifluoronitrobenzeneHCID 3197713H-Pyrazol-3-one, 2,4-dihydro-5-methyl-

Product 1

HCID 178624103-(3-Fluoro-4-nitrophenyloxy)-5-methylpyrazoleYield 12.8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

Potassium carbonate (3.46 g, 25.0 mmol) and 2,4-difluoronitrobenzene (7.95 g, 50.0 mmol) were added to a solution of 3-hydroxy-5-methylpyrazole (4.91 g, 50.0 mmol) in DMSO (80 ml) at room temperature, and the mixture was stirred at room temperature overnight. After completion of the reaction, the reaction mixture was poured into 1N hydrochloric acid (100 ml) and extracted with ethyl acetate (100 ml×2). An organic layer was washed with water (100 ml×2), dried over anhydrous magnesium sulfate and filtered to remove magnesium sulfate, and the solvent was distilled off from the filtrate under reduced pressure. The resultant crude product was purified with a silica gel column (ethyl acetate/hexane=1/3), to give a yellow solid of 3-(3-fluoro-4-nitrophenyloxy)-5-methylpyrazole (1.52 g, yield: 12.8%) [mp: 80-83° C.; 1H-NMR (CDCl3, TMS, ppm): δ 2.33 (d, J=0.5 Hz, 3H), 5.77 (d, J=0.5 Hz, 1H), 6.96-7.03 (m, 2H), 8.06-8.13 (m, 1H), 10.03 (br s, 1H)] and a yellow solid of 3-(5-fluoro-2-nitrophenyloxy)-5-methylpyrazole (0.97 g, yield: 8.2%) [mp: 95-97° C.; 1H-NMR (CDCl3, TMS, ppm): δ 2.31 (s, 3H), 5.77 (s, 1H), 6.90 (ddd, J=2.7, 5.8 and 9.1 Hz, 1H), 7.01 (dd, J=2.7 and 9.6 Hz, 1H), 8.03 (dd, J=5.8 and 9.1 Hz, 1H), 9.86 (br s, 1H)].

Workup

  1. customAfter completion of the reaction
  2. extractionextracted with ethyl acetate (100 ml×2)
  3. washAn organic layer was washed with water (100 ml×2)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customto remove magnesium sulfate
  7. distillationthe solvent was distilled off from the filtrate under reduced pressure
  8. customThe resultant crude product was purified with a silica gel column (ethyl acetate/hexane=1/3)

Sources & evidence

ORD record
ord-f966473047404a9689e6a24ce2020e7e
Source dataset
uspto-grants-2010_04
Patent number
US07700786B2

Reaction notes

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