Dimethylformamide → ethyl 4-chloro-3-formyl-5-methyl-1H-pyrrole-2-carboxylate

HRID 1948346Notes

Reaction equation

HRID 1948346 reaction equation
O=P(Cl)(Cl)Cl.CN([CH:9]=[O:10])C.[Cl:11][C:12]1[CH:13]=[C:14]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[NH:15][C:16]=1[CH3:17].C([O-])(=O)C.[Na+]>ClCCCl.O>[Cl:11][C:12]1[C:13]([CH:9]=[O:10])=[C:14]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[NH:15][C:16]=1[CH3:17]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 517045Sodium AcetateHCID 66707189ethyl 4-chloro-5-methyl-1H-pyrrole-2-carboxylate

Product 1

HCID 86643343ethyl 4-chloro-3-formyl-5-methyl-1H-pyrrole-2-carboxylateYield 30.7%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 962WaterSolvent

Procedure

POCl3 in 1,2-dichloroethane (14 mL) was slowly added to a solution of DMF (4.37 mL, 59.79 mmol) in 1,2-dichloroethane (10 mL). The reaction mixture was stirred for 15 min and then Intermediate 7 (2.04 g, 10.87 mmol) was added. The reaction mixture was heated at reflux for 3 h and then cooled to room temperature. The reaction mixture was treated with sodium acetate (10 g) in water (25 mL) and stirred for 1 h. The mixture was extracted with methylene chloride, washed with water, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 2:1 hexanes/ethyl acetate) gave the desired compound (720 mg).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 3 h
  3. stirringstirred for 1 h
  4. extractionThe mixture was extracted with methylene chloride
  5. washwashed with water
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification by flash column chromatography (silica, 2:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-241e38d15191409aaa061f430f68e776
Source dataset
uspto-grants-2013_03
Patent number
US08399489B2

Reaction notes

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