Ethyl bromoacetate → Diethyl 3-methyl-6H-thieno[2,3-b]pyrrole-2,5-dicarboxylate

HRID 365113Notes

Reaction equation

HRID 365113 reaction equation
[C:1]([NH:4][C:5]1[S:6][C:7]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:8]([CH3:12])[C:9]=1[C:10]#N)(=O)[CH3:2].[C:18](OCC)(=[O:20])[CH3:19].BrCC(OCC)=[O:27].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:16]([O:15][C:13]([C:7]1[S:6][C:5]2[NH:4][C:1]([C:2]([O:20][CH2:18][CH3:19])=[O:27])=[CH:10][C:9]=2[C:8]=1[CH3:12])=[O:14])[CH3:17]

Participants

6

Reactant 4

HCID 7748Ethyl bromoacetateHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 90296Ethyl 5-acetamido-4-cyano-3-methylthenoate

Product 1

HCID 15591622Diethyl 3-methyl-6H-thieno[2,3-b]pyrrole-2,5-dicarboxylate

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

1 mole of 2-acetamido-3-cyano-5-ethoxycarbonyl-4-methylthiophene (prepared according to the method described by Gewald K. et al., Chem. Ber. (1966), 99, p. 94 and 2712, from ethyl acetate) is brought to reflux for 24 hours in 1.6 l of acetone with 187 g of ethyl bromoacetate and 250 g of potassium carbonate. Subsequently, the mixture is precipitated in 6 liters of an ice-water mixture (1:1). The whole is vigorously stirred, the resulting precipitate is filtered, dried with air, washed with 500 ml of an iced mixture of water and ethanol (60:40), dried again, and finally washed with 700 ml of a mixture of cyclohexane and benzene (6:1). The resulting product (320 g-0.95 mole) is then stirred in 1.2 liters of H2SO4 at 30% maintained at a temperature of less than 10° C., in a current of nitrogen. 85 g of potassium nitrite in 180 ml of water are progressively added whilst maintaining the temperature. When the addition is complete, stirring is continued for a few minutes, then 7.2 liters of an ice-water mixture are added. The whole is stirred vigorously. The yellow precipitate obtained is briefly suction-filtered and rinsed with water until almost neutral. It is then brought to reflux in 3 liters of ethanol until the evolution of nitrogen is complete. Subsequently, the reaction mixture is concentrated to 1 liter by distillation, 300 ml of water are added and the whole is stirred vigorously. Once crystallisation is complete, the precipitate is filtered and dried. In this manner 205 g (0.73 mole) of 2,5-diethoxycarbonyl 3-methyl-thieno[2,3-b]pyrrole are obtained, m.p.: 139° C. The following was prepared in the same manner:

Workup

  1. customSubsequently, the mixture is precipitated in 6 liters of an ice-water mixture (1:1)
  2. filtrationthe resulting precipitate is filtered
  3. customdried with air
  4. washwashed with 500 ml of an iced mixture of water and ethanol (60:40)
  5. customdried again
  6. washfinally washed with 700 ml of a mixture of cyclohexane and benzene (6:1)
  7. stirringThe resulting product (320 g-0.95 mole) is then stirred in 1.2 liters of H2SO4 at 30%
  8. temperaturemaintained at a temperature of less than 10° C.
  9. addition85 g of potassium nitrite in 180 ml of water are progressively added
  10. temperaturewhilst maintaining the temperature
  11. additionWhen the addition
  12. stirringstirring
  13. waitis continued for a few minutes
  14. addition7.2 liters of an ice-water mixture are added
  15. stirringThe whole is stirred vigorously
  16. customThe yellow precipitate obtained
  17. filtrationis briefly suction-filtered
  18. washrinsed with water until almost neutral
  19. temperatureto reflux in 3 liters of ethanol until the evolution of nitrogen
  20. concentrationSubsequently, the reaction mixture is concentrated to 1 liter by distillation, 300 ml of water
  21. additionare added
  22. stirringthe whole is stirred vigorously
  23. customOnce crystallisation
  24. filtrationthe precipitate is filtered
  25. customdried

Sources & evidence

ORD record
ord-4271f4e17d6546bfb9a0f305934bdaba
Source dataset
uspto-grants-1986_08
Patent number
US04608384

Reaction notes

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