Sulfuric Acid → Methyl 5-Methoxy-2-thiophenecarboxylate

HRID 1961241Notes

Reaction equation

HRID 1961241 reaction equation
[CH3:1][O:2][C:3]1[S:7][C:6]([C:8]([OH:10])=[O:9])=[CH:5][CH:4]=1.OS(O)(=O)=O.[C:16]([O-])(O)=O.[Na+].[OH-].[Na+]>CO>[CH3:1][O:2][C:3]1[S:7][C:6]([C:8]([O:10][CH3:16])=[O:9])=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 51881195-Methoxythiophene-2-carboxylic acid

Product 1

HCID 12646617Methyl 5-Methoxy-2-thiophenecarboxylateYield 56%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To a 200 mL round-bottomed flask fitted with a condenser was added 5-(methyloxy)-2-thiophenecarboxylic acid (1.3 g, 8.22 mmol) in Methanol (40 mL). H2SO4 (5 mL, 94 mmol) was added slowly at room temperature and the reaction stirred at 50° C. overnight. The mixture was cooled to 0° C. and sat. NaHCO3 was added to neutral pH followed by 5N NaOH to pH 10. The mixture was partitioned between H2O/CHCl3 and the organic phase was separated and dried over Na2SO4. The solution was adsorbed onto silica and purified via column chromatography (5-50% EtOAc/Hexanes) affording the title compound (827 mg, 4.56 mmol, 56%): LC-MS (ES) m/z=173 (M+H)+.

Workup

  1. customTo a 200 mL round-bottomed flask fitted with a condenser
  2. temperatureThe mixture was cooled to 0° C.
  3. customThe mixture was partitioned between H2O/CHCl3
  4. customthe organic phase was separated
  5. dry with materialdried over Na2SO4
  6. custompurified via column chromatography (5-50% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-172c02861f7f4169bf71a3d9e5def179
Source dataset
uspto-grants-2013_04
Patent number
US08410158B2

Reaction notes

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