Acetic Acid → HCID 57559705, compound

HRID 1723955Notes

Reaction equation

HRID 1723955 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([OH:7])=[O:6].[CH:12]([O-:17])([O-])[O:13][CH2:14][CH3:15].[N+:18]([CH2:21][C:22](OCC)=O)([O-])=O.[C:27](O)(=O)C>[Fe]>[CH2:14]([O:13][C:12]([C:21]1[N:18]=[CH:27][N:1]([C:2]2[CH:3]=[C:4]([C:5]([OH:7])=[O:6])[CH:8]=[CH:9][C:10]=2[CH3:11])[CH:22]=1)=[O:17])[CH3:15]

Participants

6

Reactant 4

HCID 176Acetic Acid2×HCID 69379Ethyl nitroacetateHCID 755683-Amino-4-methylbenzoic acidHCID 53630039Ethylorthoformate2×

Product 1

HCID 57559705HCID 57559705, compoundYield 21.3%

Reagents, catalysts & solvents 1

HCID 23925IronCatalyst2×

Conditions

Temperature
85 °C

Procedure

A slurry of 3-amino-4-methylbenzoic acid (5.00 g, 33.1 mmol), ethyl orthoformate (5.94 mL), ethyl nitroacetate (3.67 mL), and acetic acid (0.2 mL) was heated to 100° C. with stirring for 3.5 h. The mixture was cooled to 85° C. and an additional 66 mL each of ethyl orthoformate and acetic acid were added followed by 5.54 g (99.2 mmol) of iron powder. The mixture was heated to reflux and stirred for 1 h, when an additional 5.54 g of iron powder was added in three portions, each portion after 1 h of stirring at reflux. The mixture was then heated for an additional 6 h before being cooled to room temperature. The mixture was filtered and the solids were washed with EtOAc. The filtrate was collected and concentrated to afford a brown semisolid. The solid was triturated with Et2O/EtOAc to provide 1.93 g (7.04 mmol, 21.3%) of 1-(5-carboxy-2-methyl-phenyl)-1H-imidazole-4-carboxylic acid ethyl ester as a tan solid.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux
  3. stirringstirred for 1 h
  4. stirringeach portion after 1 h of stirring
  5. temperatureat reflux
  6. temperatureThe mixture was then heated for an additional 6 h
  7. temperaturebefore being cooled to room temperature
  8. filtrationThe mixture was filtered
  9. washthe solids were washed with EtOAc
  10. customThe filtrate was collected
  11. concentrationconcentrated
  12. customto afford a brown semisolid
  13. customThe solid was triturated with Et2O/EtOAc

Sources & evidence

ORD record
ord-79d7e0f443d04b72a11140cc81f4c7c9
Source dataset
uspto-grants-2009_02
Patent number
US07485657B2

Reaction notes

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