Methanol → 7-Methoxybenzo[b]thiophene-2-carboxylic acid

HRID 2183661Notes

Reaction equation

HRID 2183661 reaction equation
CN(C)[C:3]([S:5][C:6]1[C:13]([O:14][CH3:15])=[CH:12][CH:11]=[CH:10][C:7]=1[CH:8]=O)=O.[OH-:17].[Na+].[OH2:19].[CH3:20]O>>[CH3:15][O:14][C:13]1[C:6]2[S:5][C:3]([C:20]([OH:19])=[O:17])=[CH:8][C:7]=2[CH:10]=[CH:11][CH:12]=1

Participants

5

Reactant 4

HCID 887MethanolHCID 962WaterHCID 14798Sodium HydroxideHCID 13123230S-(2-Formyl-6-methoxyphenyl) dimethylcarbamothioate

Product 1

HCID 8217517-Methoxybenzo[b]thiophene-2-carboxylic acid

Procedure

A mixture of 2-(N,N-dimethylcarbamoylthio)-3-methoxybenzaldehyde (6.7 g), sodium hydroxide (1.4 g), water (13 ml) and methanol (27 ml) was heated under reflux under nitrogen for 1 hour then cooled to ambient temperature and washed with dichloromethane (20 ml). Water (10 ml), methanol (10 ml) and sodium chloroacetate (3.25 g) were added, the mixture was heated under reflux for 8 hours, then it was cooled to ambient temperature and acidified by the addition of 5M hydrochloric acid (15 ml). The product was extracted into dichloromethane (3×30 ml), then the combined extracts were dried (MgSO4) and the solvent was removed in vacuo. The resulting crude (2-formyl-6-methoxyphenylthio)acetic acid (3 g) was diluted with 5M aqueous sodium hydroxide solution then the mixture was heated under reflux for 3.5 hours, cooled to ambient temperature and added dropwise to stirred 5M hydrochloric acid (150 ml). The resulting solid was collected by filtration, washed with water (40 ml) and crystallised from a 3:1 mixture of methanol and water (250 ml) to give 7-methoxybenzo[b]thiophene-2-carboxylic acid (1.9 g) as a pale pink solid which was used without further purification.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux under nitrogen for 1 hour
  3. washwashed with dichloromethane (20 ml)
  4. additionWater (10 ml), methanol (10 ml) and sodium chloroacetate (3.25 g) were added
  5. temperaturethe mixture was heated
  6. temperatureunder reflux for 8 hours
  7. temperatureit was cooled to ambient temperature
  8. additionacidified by the addition of 5M hydrochloric acid (15 ml)
  9. extractionThe product was extracted into dichloromethane (3×30 ml)
  10. dry with materialthe combined extracts were dried (MgSO4)
  11. customthe solvent was removed in vacuo
  12. additionThe resulting crude (2-formyl-6-methoxyphenylthio)acetic acid (3 g) was diluted with 5M aqueous sodium hydroxide solution
  13. temperaturethe mixture was heated
  14. temperatureunder reflux for 3.5 hours
  15. temperaturecooled to ambient temperature
  16. additionadded dropwise
  17. filtrationThe resulting solid was collected by filtration
  18. washwashed with water (40 ml)
  19. customcrystallised from a 3:1 mixture of methanol and water (250 ml)

Sources & evidence

ORD record
ord-586ab96b1b104e9587334fa04093c580
Source dataset
uspto-grants-2005_05
Patent number
US06900216B2

Reaction notes

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