p-Toluenesulfonic acid → HCID 18366585, compound

HRID 379575Notes

Reaction equation

HRID 379575 reaction equation
C([C:3]1[C:4]([C:9]([OH:11])=[O:10])=[C:5]([NH2:8])[S:6][CH:7]=1)C.[C:12]1(C)[CH:17]=CC(S(O)(=O)=O)=C[CH:13]=1.CO[C:25](OC)(C)[CH3:26].C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[CH3:13][CH:12]([NH:8][C:5]1[S:6][CH:7]=[CH:3][C:4]=1[C:9]([O:11][CH2:25][CH3:26])=[O:10])[CH3:17]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 64952,2-DimethoxypropaneHCID 516892Sodium BicarbonateHCID 22182433Ethyl 2-amino-3-carboxythiophene

Product 1

HCID 18366585HCID 18366585, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of ethyl 2-aminothiophene-3-carboxylic acid (Chem.Ber.; 1965; 98; 3571-3577, 98.8 g), 4-toluenesulfonic acid (1 g) and 2,2-dimethoxypropane (158 ml) in anhydrous toluene (650 ml) was heated at reflux under nitrogen for 5 hours. The solution was allowed to cool and was then added to saturated aqueous sodium bicarbonate solution (500 ml) and extracted with ether (500 ml). The organic extracts were dried over anhydrous magnesium sulfate, filtered and evaporated. The residual oil was dissolved in ethanol (250 ml) containing sodium borohydride (8 g). The mixture was stirred for 3 days and then further sodium borohydride (8 g) was added. The mixture was stirred for 1 further day, then sodium borohydride (4 g) was added. After a further 2 days stirring, saturated aqueous sodium bicarbonate solution (750 ml) was added and the mixture was extracted with ether (2×750 ml). The organic extracts were dried over anhydrous magnesium sulfate, filtered and evaporated. The residual oil was purified by column chromatography over silica, eluting with dichloromethane/isohexane (1:1) to give the subtitle compound (24.65 g) as an oil.

Workup

  1. temperatureat reflux under nitrogen for 5 hours
  2. temperatureto cool
  3. extractionextracted with ether (500 ml)
  4. dry with materialThe organic extracts were dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. dissolutionThe residual oil was dissolved in ethanol (250 ml)
  8. additioncontaining sodium borohydride (8 g)
  9. additionfurther sodium borohydride (8 g) was added
  10. stirringThe mixture was stirred for 1 further day
  11. additionsodium borohydride (4 g) was added
  12. stirringAfter a further 2 days stirring
  13. additionsaturated aqueous sodium bicarbonate solution (750 ml) was added
  14. extractionthe mixture was extracted with ether (2×750 ml)
  15. dry with materialThe organic extracts were dried over anhydrous magnesium sulfate
  16. filtrationfiltered
  17. customevaporated
  18. customThe residual oil was purified by column chromatography over silica
  19. washeluting with dichloromethane/isohexane (1:1)

Sources & evidence

ORD record
ord-4826df902f4547c9b78f593359d6d7ed
Source dataset
uspto-grants-2001_10
Patent number
US06300334B1

Reaction notes

Loading…