Acetone → 5-(4-methoxyphenyl)thiophene-2-carboxylic Acid

HRID 612842Notes

Reaction equation

HRID 612842 reaction equation
C([Li])CCC.[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)=[CH:10][CH:9]=1.[C:19](=[O:21])=[O:20].CC(C)=O>CCOCC>[CH3:6][O:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[S:15][C:16]([C:19]([OH:21])=[O:20])=[CH:17][CH:18]=2)=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 180AcetoneHCID 280Carbon Dioxide2×HCID 27694252-(4-methoxyphenyl)thiopheneHCID 178418339Butyllithium

Product 1

HCID 27641305-(4-methoxyphenyl)thiophene-2-carboxylic AcidYield 50%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a solution of 6.3 mL of n-butyllithium (2.5 M solution in hexane) in 50 mL of dry ether is added a solution of 3.0 g (15.8 mmol) of 2-(4-methoxyphenyl)thiophene in 20 mL of dry ether under N2 atmosphere. The mixture is stirred at room temperature for 3 hours and then heated at reflux for 30 minutes. After the reaction mixture is cooled to -78° C. with dry ice and acetone bath, dry CO2 gas is bubbled through the reaction mixture for 3 hours and the resulting solution is stirred at room temperature overnight. The reaction mixture is diluted with 200 mL of chloroform, washed with 1% HCl solution (200 mL) and with water (2×200 mL). The separated organic layer is dried over anhydrous Na2SO4 and concentrated under reduced pressure to give 1.8 g (50%) of 5-(4-methoxyphenyl)-2-thienoic acid.

Workup

  1. temperatureheated
  2. temperatureat reflux for 30 minutes
  3. customis bubbled through the reaction mixture for 3 hours
  4. stirringthe resulting solution is stirred at room temperature overnight
  5. additionThe reaction mixture is diluted with 200 mL of chloroform
  6. washwashed with 1% HCl solution (200 mL) and with water (2×200 mL)
  7. dry with materialThe separated organic layer is dried over anhydrous Na2SO4
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-3d357b7a57e94eb0bfddfb7e74e7490a
Source dataset
uspto-grants-1999_12
Patent number
US06005113

Reaction notes

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