Carbon Dioxide → 4-Methoxy-2-thiophenecarboxylic acid ethyl ester

HRID 357750

Reaction equation

HRID 357750 reaction equation
CO[C:3]1C=CS[CH:4]=1.[CH2:8]([Li])[CH2:9]CC.C(=O)=O.[CH3:16][O:17][C:18]1[CH:22]=[CH:21][S:20][C:19]=1[C:23]([OH:25])=[O:24].[CH3:26][O:27][C:28]1[CH:29]=[C:30]([C:33]([OH:35])=[O:34])[S:31][CH:32]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.CN(C)C=O.O.C(OCC)C>[CH2:3]([O:34][C:33]([C:30]1[S:31][CH:32]=[C:28]([O:27][CH3:26])[CH:29]=1)=[O:35])[CH3:4].[CH2:8]([O:24][C:23]([C:19]1[S:20][CH:21]=[CH:22][C:18]=1[O:17][CH3:16])=[O:25])[CH3:9]

Participants

12

Reactant 6

HCID 280Carbon DioxideHCID 11430Potassium CarbonateHCID 1402493-MethoxythiopheneHCID 14834753-Methoxythiophene-2-carboxylic acidHCID 126466194-Methoxythiophene-2-carboxylic acidHCID 178418339Butyllithium

Product 2

HCID 537246764-Methoxy-2-thiophenecarboxylic acid ethyl esterHCID 54203274HCID 54203274, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

3-Methoxythiophene (4.0 ml) was dissolved in tetrahydrofuran (50 ml), and the mixture was cooled to -78° C. n-Butyllithium (1.6M in hexane, 19.5 ml) was slowly added dropwise, and the mixture was stirred at the same temperature for 1 hour. The mixture was poured into a mixture of dry ice and diethyl ether, and warmed to room temperature with stirring. The solvent was distilled off, and the residue was acidified with 1N hydrochloric acid and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give a mixture of 3-methoxy-2-thiophenecarboxylic acid and 4-methoxy-2-thiophenecarboxylic acid (6.0 g). This mixture was dissolved in N,N-dimethylformamide (50 ml), and iodothane (3.0 ml) and potassium carbonate (5.25 g) were added. The mixture was stirred at room temperature for 15 hours, poured into water and extracted with diethyl ether. The extract was washed with 5% aqueous potassium hydrogen sulfate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and the desired fractions were concentrated under reduced pressure to give 4-methoxy-2-thiophenecarboxylic acid ethyl ester (2.69 g) and 3-methoxy-2-thiophenecarboxylic acid ethyl ester (3.98 g). 4-Methoxy-2-thiophenecarboxylic acid ethyl ester (2.69 g) was dissolved in a mixture of ethanol (25 ml) and tetrahydrofuran (25 ml), and 1N aqueous sodium hydroxide (22 ml) was added. The mixture was stirred at room temperature for 3 hours and washed with diethyl ether. The aqueous layer was acidified with 1N hydrochloric acid and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 4-methoxy-2-thiophenecarboxylaic acid (2.11 g) as crystals.

Workup

  1. additionwas slowly added dropwise
  2. stirringwith stirring
  3. distillationThe solvent was distilled off
  4. extractionextracted with ethyl acetate
  5. dry with materialThe extract was dried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto give
  8. stirringThe mixture was stirred at room temperature for 15 hours
  9. extractionextracted with diethyl ether
  10. washThe extract was washed with 5% aqueous potassium hydrogen sulfate
  11. dry with materialdried over anhydrous magnesium sulfate
  12. concentrationconcentrated under reduced pressure
  13. concentrationthe desired fractions were concentrated under reduced pressure

Sources & evidence

ORD record
ord-5491d0276a85450b8be233b31747eab1
Source dataset
uspto-grants-1998_11
Patent number
US05840917

Linked notes

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