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

HRID 1930791Notes

Reaction equation

HRID 1930791 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-dihydro-thiophene-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 organic extracts washed with brine (1×10 mL), dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography (5% MeOH/DCM) and recrystallised 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 organic extracts washed with brine (1×10 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (5% MeOH/DCM)
  8. customrecrystallised from EtOAc/hexane

Sources & evidence

ORD record
ord-849c02776d634cc48d5aa743c7f348ee
Source dataset
uspto-grants-2012_05
Patent number
US08188134B2

Reaction notes

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