Ammonium formate → methyl 4H-thieno(3,2-b)pyrrole-2-carboxylate

HRID 1363321Notes

Reaction equation

HRID 1363321 reaction equation
CN(C)[CH:3]=[CH:4][C:5]1[S:9][C:8]([C:10]([O:12][CH3:13])=[O:11])=[CH:7][C:6]=1[N+:14]([O-])=O.C([O-])=O.[NH4+]>CO.[Pd]>[S:9]1[C:5]2[CH:4]=[CH:3][NH:14][C:6]=2[CH:7]=[C:8]1[C:10]([O:12][CH3:13])=[O:11]

Participants

5

Reactant 2

HCID 2723923Ammonium formate3×HCID 72053195Methyl 5-(2-dimethylaminovinyl)-4-nitrothiophene-2-carboxylate

Product 1

HCID 12110979methyl 4H-thieno(3,2-b)pyrrole-2-carboxylateYield 16%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst3×HCID 887MethanolSolvent

Procedure

To a solution of methyl 5-(2-dimethylaminovinyl)-4-nitro-thiophene-2-carboxylate (0.698 g, 2.73 mmol) in MeOH (15.0 mL) were added ammonium formate (0.332 g, 5.26 mmol) and Pd/C (33.2 mg, 10% by weight). The mixture was refluxed for 6 h. Additional ammonium formate (0.664 g, 10.53 mmol) was added to the reaction and the mixture was refluxed for 20 h. Additional ammonium formate (0.664 g, 10.53 mmol) and Pd/C (0.1 g, 30% by weight) were added and the reaction mixture was refluxed for another 8 h. Additional Pd/C (0.1 g, 30% by weight) was added and the mixture was refluxed for another 16 h. The reaction was cooled and filtered through a Celite® plug. The filtrate was concentrated in vacuo, taken up in EtOAc (0.2 L) and washed with water, saturated aq NaCl, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by HPLC to obtain methyl 4H-thieno[3,2-b]pyrrole-2-carboxylate as a yellow solid (0.078 g, 16%). 1H NMR (400 MHz, CDCl3) δ (ppm) 8.40 (s, 1H) 7.71 (s, 1H) 7.20 (t, J=2.7 Hz, 1H) 6.50 (m, 1H), 3.90 (s, 3H).

Workup

  1. temperatureThe mixture was refluxed for 6 h
  2. temperaturethe mixture was refluxed for 20 h
  3. temperaturethe reaction mixture was refluxed for another 8 h
  4. temperaturethe mixture was refluxed for another 16 h
  5. temperatureThe reaction was cooled
  6. filtrationfiltered through a Celite® plug
  7. concentrationThe filtrate was concentrated in vacuo
  8. washwashed with water, saturated aq NaCl
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe crude product was purified by HPLC

Sources & evidence

ORD record
ord-69233f5d2a0c42959e91f927551ca542
Source dataset
uspto-grants-2011_02
Patent number
US07884124B2

Reaction notes

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