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

HRID 2076267Notes

Reaction equation

HRID 2076267 reaction equation
C(O)(=O)C.[CH:5]([N:7]([CH2:20][C:21](=O)[CH3:22])[C:8]1[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][C:9]=1[O:18][CH3:19])=O.C([O-])(=O)C.[NH4+:28].N>C(OCC)(=O)C>[CH3:19][O:18][C:9]1[CH:10]=[C:11]([CH:16]=[CH:17][C:8]=1[N:7]1[CH:20]=[C:21]([CH3:22])[N:28]=[CH:5]1)[C:12]([O:14][CH3:15])=[O:13]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 222AmmoniaHCID 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

Procedure

An acetic acid (255 mL) solution of methyl 4-[formyl-(2-oxopropyl)amino]-3-methoxybenzoate (118 g) and ammonium acetate (172 g) was heat-stirred at 140° C. for one hour. After the completion of reaction, the reaction liquid was neutralized with aqueous ammonia under cooling with ice. Ethyl acetate was added to the reaction liquid to separate an organic layer. The resultant organic layer was dried with anhydrous magnesium sulfate and filtered on a silica gel pad, followed by concentrating the filtrate under reduced pressure. To the residue were added tertiary-butyl methyl ether and heptane, followed by collecting the precipitated solid by filtration before washing with a heptane solution of 50% tertiary-butyl methyl ether. The resultant solid was air-dried overnight to provide 68.4 g of the title compound. In addition, the crystallizing mother liquor was concentrated under reduced pressure, followed by purifying the residue using silica gel column chromatography (elution solvent: a heptane-ethyl acetate system) to provide 22.3 g of the title compound.

Workup

  1. customAfter the completion of reaction
  2. customthe reaction liquid
  3. temperatureunder cooling with ice
  4. customto separate an organic layer
  5. dry with materialThe resultant organic layer was dried with anhydrous magnesium sulfate
  6. filtrationfiltered on a silica gel pad
  7. concentrationby concentrating the filtrate under reduced pressure
  8. additionTo the residue were added tertiary-butyl methyl ether and heptane
  9. customby collecting the precipitated solid
  10. filtrationby filtration
  11. washbefore washing with a heptane solution of 50% tertiary-butyl methyl ether
  12. customThe resultant solid was air-dried overnight

Sources & evidence

ORD record
ord-5054a7961ad24a6b95ad6df792287aa4
Source dataset
uspto-grants-2011_04
Patent number
US07923563B2

Reaction notes

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