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

HRID 650045Notes

Reaction equation

HRID 650045 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, υ=cm−1) 3430, 1726, 1512, 1232, 1068; 1H NMR (300 MHz, DMSO-d6) δ 3.80 (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-a4a1cd95eff74bd8966222688d4f0b46
Source dataset
uspto-grants-2001_08
Patent number
US06271249B1

Reaction notes

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