Imidazole → 3-Hydroxy-5-imidazol-1-yl-thiophene-2-carboxylic acid methyl ester

HRID 1171162Notes

Reaction equation

HRID 1171162 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[CH3:6][O:7][C:8]([C:10]1(Cl)[C:14](=[O:15])[CH:13]=[CH:12][S:11]1)=[O:9]>C(Cl)Cl>[CH3:6][O:7][C:8]([C:10]1[S:11][C:12]([N:1]2[CH:5]=[CH:4][N:3]=[CH:2]2)=[CH:13][C:14]=1[OH:15])=[O:9]

Participants

4

Reactant 2

HCID 795ImidazoleHCID 15588102Methyl 2-chloro-3-oxo-2,3-dihydrothiophene-2-carboxylate

Product 1

HCID 546956113-Hydroxy-5-imidazol-1-yl-thiophene-2-carboxylic acid methyl esterYield 59.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Imidazole (710 mg, 10.4 mmol, 2 Eq.) and 2-Chloro-3-oxo-2,3-dihydrothiophene-2-carboxylic acid methyl ester (1.0 g, 5.19 mmol, 1.0 Eq.) were dissolved in anhydrous DCM (25 mL) and stirred at ambient temperature for 18 hours. The crude reaction mixture was partitioned between EtOAc (50 mL) and brine (50 mL), The aqueous phase was extracted with EtOAc (3×20 mL) and the combined organice extracts washed with brine (1×10 mL), dried (Na2SO4) and concentrated in vacuo. The residue was purifed by column chromatography (5% MeOH/DCM) and recrystalised from EtOAc/hexane to give the sub-title compound as a yellow powder (692 mg, 3.09 mmol 59%); 1H NMR (400 MHz, d-6 DMSO) δ 3.77 (3H, s), 7.02 (1H, s), 7.14 (1H, d), 7.74 (1H, d), 8.28 (1H, d), 10.82 (1H, br s).

Workup

  1. customThe crude reaction mixture
  2. customwas partitioned between EtOAc (50 mL) and brine (50 mL)
  3. extractionThe aqueous phase was extracted with EtOAc (3×20 mL)
  4. washthe combined organice extracts washed with brine (1×10 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customrecrystalised from EtOAc/hexane

Sources & evidence

ORD record
ord-b611840adc224d1ebc4fb07eb14c0cc2
Source dataset
uspto-grants-2010_11
Patent number
US07829590B2

Reaction notes

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