Acetic Acid → Methyl 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzoate

HRID 1446444Notes

Reaction equation

HRID 1446444 reaction equation
C(O)(=O)C.[CH3:5][O:6][C:7](=[O:23])[C:8]1[CH:13]=[CH:12][C:11]([N:14]([CH:19]=O)[CH2:15][C:16](=O)[CH3:17])=[C:10]([O:21][CH3:22])[CH:9]=1.C([O-])(=O)C.[NH4+:28]>C(OCC)(=O)C>[CH3:5][O:6][C:7](=[O:23])[C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH:15]=[C:16]([CH3:17])[N:28]=[CH:19]2)=[C:10]([O:21][CH3:22])[CH:9]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 517165Ammonium AcetateHCID 86602464Methyl 4-[formyl-(2-oxopropyl)amino]-3-methoxybenzoate

Product 1

HCID 27282443Methyl 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzoateYield 62.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

An acetic acid (255 mL) solution of 4-(formyl-(2-oxopropyl)amino)-3-methoxybenzoic acid methyl ester (118 g) and ammonium acetate (172 g) was heated under stirring at 140° C. for 1 hour. The reaction solution was neutralized with an ammoniac solution under ice-cooling after the reaction completed. Ethyl acetate was added to the reaction solution, and the organic layer was partitioned. The obtained organic layer was filtered with a silica gel pad after dried over anhydrous magnesium sulfate, and the filtrate was concentrated under reduced pressure. Tert-butylmethyl ether and heptane were added to the residue and the deposited solids were separated by filtering and washed with a 50% heptane solution of tert-butylmethyl ether. 68.4 g of the title compound was obtained by air-drying the obtained solids overnight. Furthermore, crystallization mother liquid was concentrated under reduced pressure, the residue was purified by silica gel column chromatography (elution solvent:heptane-ethyl acetate system), and 22.3 g of the title compound was obtained.

Workup

  1. temperaturecooling after the reaction
  2. customthe organic layer was partitioned
  3. filtrationThe obtained organic layer was filtered with a silica gel pad
  4. dry with materialafter dried over anhydrous magnesium sulfate
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. additionTert-butylmethyl ether and heptane were added to the residue
  7. customthe deposited solids were separated
  8. filtrationby filtering
  9. washwashed with a 50% heptane solution of tert-butylmethyl ether

Sources & evidence

ORD record
ord-4cce8c319a2944e7ba23917192aa4ba0
Source dataset
uspto-grants-2010_02
Patent number
US07667041B2

Reaction notes

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