Methanol → Methyl 5-formylpyrrole-3-carboxylate

HRID 588511Notes

Reaction equation

HRID 588511 reaction equation
[Cl-].[NH:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[CH:7]=[N+](C)C.[Cl-].[Cl-].[Cl-].[Al+3].ClC(Cl)(Cl)[C:17](Cl)=[O:18].[CH3:22][O-:23].[Na+].C[OH:26]>ClCCCl>[CH:7]([C:3]1[NH:2][CH:6]=[C:5]([C:22]([O:18][CH3:17])=[O:23])[CH:4]=1)=[O:26]

Participants

7

Reactant 5

HCID 887MethanolHCID 6420Trichloroacetyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 10942334Sodium MethoxideHCID 12676265N-((1H-pyrrol-2-yl)methylene)-N-methylmethanaminium chloride

Product 1

HCID 579027Methyl 5-formylpyrrole-3-carboxylateYield 60%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of N-((1H-pyrrol-2-yl)methylene)-N-methylmethanaminium chloride (45.0 g, 0.279 mol), aluminum trichloride (83.7 g, 0.63 mol) in DCE (90 mL) under nitrogen was added 2,2,2-trichloroacetyl chloride (32.4 mL, 0.093 mol). The mixture was heated to reflux for 4 h. After cooled to rt, MeOH (100 mL) was added followed by sodium methoxide solution [prepared with sodium (45.0 g, 1.98 mol) and MeOH (180 mL)]. The resulting mixture was then stirred at rt for 2 h. The solvent was then removed and the resulting residue was dissolved in water (100 mL), neutralized with 1 N HCl, and extracted with EtOAc (3×400 mL). The combined organic phases were washed with brine, dried, and concentrated to give methyl 5-formyl-1H-pyrrole-3-carboxylate (30.0 g, 60%). 1H NMR (DMSO-d6, 400 MHz) δ 12.62 (s, 1H), 9.48 (s, 1H), 7.66 (s, 1H), 7.30 (s, 1H), 3.67 (s, 3H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 4 h
  3. customThe solvent was then removed
  4. dissolutionthe resulting residue was dissolved in water (100 mL)
  5. extractionextracted with EtOAc (3×400 mL)
  6. washThe combined organic phases were washed with brine
  7. customdried
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-98e98f93aeed4cba862a1257d77ab793
Source dataset
uspto-grants-2016_01
Patent number
US09227951B2

Reaction notes

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