Chlorosuccinimide → 2-Chloro-6H-thieno[2,3-b]pyrrole-5-carboxylic acid ethyl ester

HRID 1368965Notes

Reaction equation

HRID 1368965 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:10][C:9]2[S:11][CH:12]=[CH:13][C:8]=2[CH:7]=1)=[O:5])[CH3:2].[Cl:14]N1C(=O)CCC1=O>C(O)(=O)C.C(Cl)(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[NH:10][C:9]2[S:11][C:12]([Cl:14])=[CH:13][C:8]=2[CH:7]=1)=[O:5])[CH3:2]

Participants

5

Reactant 2

HCID 31398ChlorosuccinimideHCID 11708220ethyl 6H-thieno[2,3-b]pyrrole-5-carboxylate

Product 1

HCID 116010652-Chloro-6H-thieno[2,3-b]pyrrole-5-carboxylic acid ethyl esterYield 48.2%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6212ChloroformSolvent

Procedure

Using a modified procedure by R. M. Kellogg et al. (J. Org. Chem., 33: 2902-290 (1968)), to a 0° C. solution of 6H-thieno[2,3-b]pyrrole-5-carboxylic acid ethyl ester (Eras, J.; Galvez, C.; Garcia, F., J. Heterocycl. Chem., 21: 215-217 (1984); 1.45 g, 7.44 mmol) in acetic acid (15 mL) and CHCl3 (15 mL) was added N-chlorosuccinimide (1.04 g, 7.81 mmol) over 2 h. The reaction mixture was slowly allowed to warm to room temperature over several hours, stirred overnight, concentrated to remove the chloroform, diluted with water, basified with 5 N NaOH, and extracted with ethyl acetate. The combined organic phases were washed with saturated aqueous NaHCO3, dried over MgSO4, and concentrated. The product was purified by chromatron chromatography (radial) using 90:10 hexanes/diethyl ether and then then then the product obtained was recrystallized using hexanes/diethyl ether (90:10). Last, the product of the recrystallization was further purified by flash column chromatography using 90:10 petroleum ether/isopropyl ether. The resulting product was obtained as a white solid (824 mg, 48%).

Workup

  1. concentrationconcentrated
  2. customto remove the chloroform
  3. additiondiluted with water
  4. extractionextracted with ethyl acetate
  5. washThe combined organic phases were washed with saturated aqueous NaHCO3
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe product was purified by chromatron chromatography (radial)
  9. customthe product obtained
  10. customwas recrystallized
  11. customLast, the product of the recrystallization
  12. customwas further purified by flash column chromatography

Sources & evidence

ORD record
ord-6d97c6576b594a7c8b35266aa74bdc80
Source dataset
uspto-grants-2003_06
Patent number
US06576653B2

Reaction notes

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