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

HRID 1363274Notes

Reaction equation

HRID 1363274 reaction equation
[S:1]1[C:5]2[NH:6][C:7]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:8][C:4]=2[CH:3]=[CH:2]1.CC(O)=O.[Cl:18]N1C(=O)CCC1=O>C(Cl)(Cl)Cl>[Cl:18][C:2]1[S:1][C:5]2[NH:6][C:7]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:8][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 31398Chlorosuccinimide2×HCID 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 66%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of ethyl 6H-thieno[2,3-b]pyrrole-5-carboxylate (0.21 g, 1.1 mmol) in CHCl3 (2.0 mL) cooled in an ice bath to 0° C., was added AcOH (glacial, 2.0 mL) followed by portionwise addition of N-chlorosuccinimide (NCS) (0.14 g, 1.1 mmol) over 2 h. After the addition of NCS was complete, the ice bath was removed and the reaction was allowed to stir at 23° C. for 5 h. After 5 h the CHCl3 was removed in vacuo and the remaining mixture was combined with aqueous 4N NaOH (10 mL) and extracted with EtOAc (3×30 mL). The combined organics were dried over Na2SO4, filtered and the solvent removed in vacuo. Purification by flash column chromatography (25% EtOAc in hexanes) afforded ethyl 2-chloro-6H-thieno[2,3-b]pyrrole-5-carboxylate (0.16 g, 66% yield).

Workup

  1. customthe ice bath was removed
  2. customAfter 5 h the CHCl3 was removed in vacuo
  3. extractionextracted with EtOAc (3×30 mL)
  4. dry with materialThe combined organics were dried over Na2SO4
  5. filtrationfiltered
  6. customthe solvent removed in vacuo
  7. customPurification by flash column chromatography (25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-353aabcd42f44d4888b4edbe0af6efe6
Source dataset
uspto-grants-2011_02
Patent number
US07884124B2

Reaction notes

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