Imidazole → HCID 66593505, compound

HRID 1091634Notes

Reaction equation

HRID 1091634 reaction equation
C(=O)([O-])[O-].[K+].[K+].Br[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[C:11]([F:18])[CH:10]=1.[NH:19]1[CH:23]=[CH:22][N:21]=[CH:20]1>C(#N)C>[F:18][C:11]1[CH:10]=[C:9]([CH:14]=[CH:13][C:12]=1[N+:15]([O-:17])=[O:16])[CH2:8][N:19]1[CH:23]=[CH:22][N:21]=[CH:20]1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 27746613-Fluoro-4-nitrobenzyl bromide

Product 1

HCID 66593505HCID 66593505, compoundYield 48.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Potassium carbonate (1.18 g, 8.54 mmol) was added to a stirred solution of 4-(bromomethyl)-2-fluoro-1-nitrobenzene (2.0 g, 8.55 mmol) and imidazole (584 mg, 8.58 mmol) in acetonitrile (40 mL), the mixture stirred at room temperature for 3.5 h, the solvent removed under reduced pressure, and the residue partitioned between water and EA. The aqueous layer was extracted three times with EA, then the combined EA layers were extracted three times with 1M hydrochloric acid. The pH of the combined aqueous layers was adjusted to 8 with 5M aqueous sodium hydroxide, and the resulting milky solution was extracted three times with EA. The EA layers were combined, washed with brine, and dried over magnesium sulfate. Filtration and concentration gave 1-(3-fluoro-4-nitrobenzyl)-1H-imidazole (914 mg), which contained about 15% of a bis-alkylated imidazole byproduct. 1-(3-Fluoro-4-nitrobenzyl)-1H-imidazole (914 mg) was treated with an ethanolic ammonia solution (2M NH3, 55 mL) in a sealed tube heated to 80° C. for 2 days. After cooling, the solvent was removed to give 5-[(1H-imidazol-1-yl)methyl]-2-nitrobenzeneamine (1.0 g) as an orange solid. 5-[(1H-Imidazol-1-yl)methyl]-2-nitrobenzeneamine (1.0 g, 4.77 mmol) was dissolved in a 10% solution of dimethylformamide in ethanol (44 mL), and 10% palladium on carbon (130 mg, 0.12 mmol) was added. The solution was degassed and stirred under a hydrogen atmosphere using a balloon for 1 day. Following degassing, the solution was diluted with MeOH and filtered through diatomaceous earth, giving 4-[(1H-imidazol-1-yl)methyl]benzene-1,2-diamine (1.08 g) as a brown oil.

Workup

  1. customthe solvent removed under reduced pressure
  2. customthe residue partitioned between water and EA
  3. extractionThe aqueous layer was extracted three times with EA
  4. extractionthe combined EA layers were extracted three times with 1M hydrochloric acid
  5. extractionthe resulting milky solution was extracted three times with EA
  6. washwashed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-32eb9d1ebac24bc0a26a04c698511b99
Source dataset
uspto-grants-2012_03
Patent number
US08129396B2

Reaction notes

Loading…