Hydrochloric Acid → Methyl 5-hydroxybenzofuran-2-carboxylate

HRID 984108Notes

Reaction equation

HRID 984108 reaction equation
[CH3:1][O:2][C:3]([C:5]1[O:6][C:7]2[CH:13]=[CH:12][C:11](SC(=O)N(C)C)=[CH:10][C:8]=2[CH:9]=1)=[O:4].[OH-].[K+].Cl.[OH:23]S(O)(=O)=O>CO.C(O)C.O>[CH3:1][O:2][C:3]([C:5]1[O:6][C:7]2[CH:13]=[CH:12][C:11]([OH:23])=[CH:10][C:8]=2[CH:9]=1)=[O:4]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1118Sulfuric AcidHCID 14797Potassium HydroxideHCID 20766008HCID 20766008, compound

Product 1

HCID 12208973Methyl 5-hydroxybenzofuran-2-carboxylateYield 95%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 19096565Water ethanolSolvent

Procedure

A solution of 5-dimethylcarbamoylsulfanyl-benzofuran-2-carboxylic acid methyl ester (0.5 g, 1.8 mmol) and potassium hydroxide (0.5 g, 12.5 mmol) in 25 ml 2:1 ethanol/water was heated at reflux for 18 hours. The reaction was then cooled, acidified with 2 M HCl, extracted 2×25 mL EtOAc, dried (Na2SO4) and the solvent removed in vacuo to give 350 mg of the crude product. The crude mixture was then refluxed overnight in 25 mL MeOH and catalytic H2SO4. The reaction was then cooled, concentrated in vacuo, taken up in EtOAc and washed with brine. The organic layer was then dried (Na2SO4) and concentrated in vacuo to give 330 mg (95%) of the title compound pure enough for subsequent use. 400 MHz 1H NMR (DMSO-d6) δ 7.66 (s, 1H), 7.62 (s, 1H), 7.57(d, 1H, J=9.0 Hz), 7.37 (d, 1H, J=9.0 Hz), 5.49 (s(br), 1H), 3.85 (s, 3H). Preparation of 5-[4-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethylsulfanyl]-benzofuran-2-carboxylic acid methyl ester (Compound 6E)

Workup

  1. temperatureat reflux for 18 hours
  2. temperatureThe reaction was then cooled
  3. extractionextracted 2×25 mL EtOAc
  4. dry with materialdried (Na2SO4)
  5. customthe solvent removed in vacuo
  6. customto give 350 mg of the crude product
  7. temperatureThe reaction was then cooled
  8. concentrationconcentrated in vacuo
  9. washwashed with brine
  10. dry with materialThe organic layer was then dried (Na2SO4)
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4271096b74c440c48911b96a5329494b
Source dataset
uspto-grants-2005_03
Patent number
US06867224B2

Reaction notes

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