4-Methylpyrazole → 4-methyl-1-(3-nitro-5-(trifluoromethyl)phenyl)-1H-pyrazole

HRID 1050147Notes

Reaction equation

F[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([N+:12]([O-:14])=[O:13])[CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:21][C:22]1[CH:23]=[N:24][NH:25][CH:26]=1>CN(C=O)C>[CH3:21][C:22]1[CH:23]=[N:24][N:25]([C:2]2[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([N+:12]([O-:14])=[O:13])[CH:3]=2)[CH:26]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of 1-fluoro-3-nitro-5-(trifluoromethyl)benzene (500 mg, 2.391 mmol) and K2CO3 (496 mg, 3.59 mmol) in DMF (3 mL) was added 4-methyl-1H-pyrazole (196 mg, 2.391 mmol) in one portion. Then the mixture stirred under N2 was heated to 110° C. and reacted for 15 h. LCMS analysis showed the starting material disappeared. The solvent was removed in vacuo. The residue was dissolved in DCM (60 mL) and washed with H2O (20 mL) and brine (20 mL). The organic layer was dried over Na2SO4, filtered and concentrated to give crude material which was purified by silica column chromatography (PE/EA=10/1 to 5/1) to afford pure product 4-methyl-1-(3-nitro-5-(trifluoromethyl)phenyl)-1H-pyrazole (500 mg, 1.678 mmol, 70.2% yield): 1H NMR (400 MHz, CD3OD): δ 8.83 (s, 1H), 8.46 (s, 1H), 8.35 (s, 1H), 8.30 (s, 1H), 7.64 (s, 1H), 2.18 (s, 3H). ES-LCMS: m/z 272.2 (M+H).

Workup

customreacted for 15 h
customThe solvent was removed in vacuo
dissolutionThe residue was dissolved in DCM (60 mL)
washwashed with H2O (20 mL) and brine (20 mL)
dry with materialThe organic layer was dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customto give crude material which
customwas purified by silica column chromatography (PE/EA=10/1 to 5/1)

Sources & evidence

ORD record: ord-5f52a61366fb4b65b5e60df8f17f4288
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382238B2

Reaction notes

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