5-Fluoro-2-nitro-4-trifluoromethyl-benzoic acid methyl ester → 1-(5-methoxycarbonyl-4-nitro-2-trifluoromethyl-phenyl)-1H-imidazole-4-carboxylic acid methyl ester

HRID 2069303Notes

Reaction equation

HRID 2069303 reaction equation
[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[C:8](F)[C:7]([C:11]([F:14])([F:13])[F:12])=[CH:6][C:5]=1[N+:15]([O-:17])=[O:16].[CH3:19][O:20][C:21]([C:23]1[N:24]=[CH:25][NH:26][CH:27]=1)=[O:22]>O1CCCC1>[CH3:19][O:20][C:21]([C:23]1[N:24]=[CH:25][N:26]([C:8]2[CH:9]=[C:4]([C:3]([O:2][CH3:1])=[O:18])[C:5]([N+:15]([O-:17])=[O:16])=[CH:6][C:7]=2[C:11]([F:14])([F:13])[F:12])[CH:27]=1)=[O:22]

Participants

4

Reactant 2

HCID 589644905-Fluoro-2-nitro-4-trifluoromethyl-benzoic acid methyl esterHCID 178418785HCID 178418785, compound2×

Product 1

HCID 589644761-(5-methoxycarbonyl-4-nitro-2-trifluoromethyl-phenyl)-1H-imidazole-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 8.00 g (29.95 mmol) of 5-fluoro-2-nitro-4-trifluoromethyl-benzoic acid methyl ester in 40 ml dry tetrahydrofuran, 5.40 g (42.00 mmol) of 1H-imidazole-4-carboxylic acid methyl ester are added. The reaction mixture is stirred at 70° C. for 48 hours (after 16 hours addition of 0.3 equivalents of 1H-imidazole-4-carboxylic acid methyl ester). Subsequently the solvent is evaporated and the light brown residue is extracted with dichloromethane. The combined organic extracts are dried, the solvent evaporated to give light purple crystals. The crude product is purified by flash-master chromatography (dichloromethane/methanol 100-90/0-10 gradient) to yield 1-(5-methoxycarbonyl-4-nitro-2-trifluoromethyl-phenyl)-1H-imidazole-4-carboxylic acid methyl ester. 1H-NMR; DMSO-d6 (400 MHz, ppm): 8.71 (s, 1H , aromatic); 8.31 (s, 1H , aromatic); 8.27 (s, 1H, imdazole); 8.09 (s, 1H, imdazole); 3.92 (s, 3H Ar-COOCH3); 3.80 (s, 3H, COOCH3); LC-MS: 374 [M+H]+; Agilent LC/MSD 1100 Series; LC-MS method: Column: SunFireC18, 4.6*50 mm, 3.5 μm; positive MS; water/acetonitril 95:5 to 5:95 in 5 min, flow: 1.5 ml/min.

Workup

  1. customSubsequently the solvent is evaporated
  2. extractionthe light brown residue is extracted with dichloromethane
  3. customThe combined organic extracts are dried
  4. customthe solvent evaporated
  5. customto give light purple crystals
  6. customThe crude product is purified by flash-master chromatography (dichloromethane/methanol 100-90/0-10 gradient)

Sources & evidence

ORD record
ord-608b5533b78744efb5222b5e1e911859
Source dataset
uspto-grants-2012_10
Patent number
US08299085B2

Reaction notes

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