Cesium carbonate → 4-methyl-1-(3-nitro-5-(trifluoromethyl)phenyl)-1H-imidazole

HRID 576154Notes

Reaction equation

[CH3:1][C:2]1[N:3]=[CH:4][NH:5][CH:6]=1.F[C:8]1[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:11]=[C:10]([N+:18]([O-:20])=[O:19])[CH:9]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH3:1][C:2]1[N:3]=[CH:4][N:5]([C:8]2[CH:13]=[C:12]([C:14]([F:16])([F:17])[F:15])[CH:11]=[C:10]([N+:18]([O-:20])=[O:19])[CH:9]=2)[CH:6]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A suspension of 4-methyl-1H-imidazole (1.178 g, 14.35 mmol) in DMF (15 mL) was added to a solution of 1-fluoro-3-nitro-5-(trifluoromethyl)benzene (2 g, 9.56 mmol) in DMF (15 mL). Cs2CO3 (6.23 g, 19.13 mmol) was added and the mixture was stirred at 80° C. for 8 h. The mixture was cooled to rt and then the solution was concentrated and distributed between EA and saturated NaHCO3 solution. The combined organic extract was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=5:1). All fractions found to contain product by TLC (PE/EA=1:1, Rf=0.5) were combined and concentrated to yield a light yellow solid of 4-methyl-1-(3-nitro-5-(trifluoromethyl)phenyl)-1H-imidazole (800 mg, 2.95 mmol, 30.8% yield): 1H NMR (400 MHz, CD3OD) δ 8.61-8.78 (m, 1H), 8.44-8.51 (m, 1H), 8.31-8.39 (m, 2H), 7.55 (s, 1H), 2.27 (s, 3H); ES-LCMS m/z 272.0 (M+H).

Workup

temperatureThe mixture was cooled to rt
concentrationthe solution was concentrated
extractionThe combined organic extract
washwas washed with brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe crude material was purified by silica column chromatography (PE/EA=5:1)
concentrationconcentrated

Sources & evidence

ORD record: ord-8841a688c6674c38aa65ef4058fb4166
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09035063B2

Reaction notes

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