Imidazole → 5-(1H-Imidazol-1-yl)-2-methoxybenzoic acid, methyl ester

HRID 362458Notes

Reaction equation

HRID 362458 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:12][CH3:13])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[NH:14]1[CH:18]=[CH:17][N:16]=[CH:15]1.C(=O)([O-])[O-].[K+].[K+].[K+].[Br-]>CN(C=O)C>[N:14]1([C:2]2[CH:3]=[CH:4][C:5]([O:12][CH3:13])=[C:6]([CH:11]=2)[C:7]([O:9][CH3:10])=[O:8])[CH:18]=[CH:17][N:16]=[CH:15]1

Participants

6

Reactant 4

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 253877Potassium BromideHCID 13297188Methyl 5-bromo-2-methoxybenzoate

Product 1

HCID 161056495-(1H-Imidazol-1-yl)-2-methoxybenzoic acid, methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Bromo-2-methoxybenzoic acid, methyl ester (5 g, 20.4 mmol), imidazole (1.4 g, 20.6 mmol), and potassium carbonate (2.9 g, 20.7 mmol) were heated to 145° C. in DMF under N2 as cuprous iodide (1.5 g, 7.9 mmol) was added in portions. The reaction was stirred at this temperature for 18 h, allowed to cool, and filtered through a celite plug. The filtered salts were washed extensively with methanol, the filtrate concentrated in vacuo, and the residue taken up in ethyl acetate, washed with water, brine, and dried. Chromatography on SiO2, elution with methanol/ethyl acetate/hexanes (1:1:3) gave 3 g (63%); IR(KBr, ν=cm-1) 3430, 1726, 1512, 1232, 1068; 1H NMR (300 MHz, DMSO-d6) δ3.80 (3H, s), 3.85 (3H, s), 7.07 (1H, s), 7.27 (1H, d, J=8.8 Hz), 7.69 (1H, s), 7.76-7.82 (2H, m) 8.18 (1H, s); MS(DCl)m/z: 233 (MH+).

Workup

  1. additionwas added in portions
  2. temperatureto cool
  3. filtrationfiltered through a celite plug
  4. washThe filtered salts were washed extensively with methanol
  5. concentrationthe filtrate concentrated in vacuo
  6. washwashed with water, brine
  7. customdried
  8. washChromatography on SiO2, elution with methanol/ethyl acetate/hexanes (1:1:3)
  9. customgave 3 g (63%)

Sources & evidence

ORD record
ord-604e46f515b649ea8dbbb123940f5be2
Source dataset
uspto-grants-1999_02
Patent number
US05869509

Reaction notes

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