Dimethylformamide → 4-(3-dimethylaminopropyl)-3,5-dimethyl-1H-pyrrole-2-carbaldehyde

HRID 2120242Notes

Reaction equation

HRID 2120242 reaction equation
CN(C)[CH:3]=[O:4].P(Cl)(Cl)(Cl)=O.[CH3:11][C:12]1[NH:13][CH:14]=[C:15]([CH3:23])[C:16]=1[CH2:17][CH2:18][CH2:19][N:20]([CH3:22])[CH3:21].[OH-].[Na+]>ClCCl>[CH3:21][N:20]([CH3:22])[CH2:19][CH2:18][CH2:17][C:16]1[C:15]([CH3:23])=[C:14]([CH:3]=[O:4])[NH:13][C:12]=1[CH3:11]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychloride2×HCID 23439033[3-(2,4-dimethyl-1H-pyrrol-3-yl)-propyl]-dimethylamine

Product 1

HCID 219257584-(3-dimethylaminopropyl)-3,5-dimethyl-1H-pyrrole-2-carbaldehydeYield 63.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To the ice-cooled solution of N,N-dimethylformamide (6.0 mL, 76 mmol) in dichloromethane (30 mL) was added phosphorus oxychloride (7.0 mL, 76 mmol) dropwise. Upon addition of phosphorus oxychloride, the reaction mixture was stirred at room temperature for 15 minutes and a solution of [3-(2,4-dimethyl-1H-pyrrol-3-yl)-propyl]-dimethyl-amine (6.8 g, 38 mmol) in dichloromethane (20 mL) was added dropwise at 0° C. The final reaction mixture was refluxed at 60° C. for 4 hours and cooled with ice bath. Ice cube was added to the reaction mixture slowly followed by addition of 2 N sodium hydroxide to adjust pH to 12. The reaction mixture was stirred at room temperature for 30 minutes and extracted with ethyl acetate. The organic-layer was washed with brine, dried over anhydrous sodium sulfate and concentrated to give crude product which was purified on a silica gel column eluting with dichloromethane-methanol-ammonium hydroxide (9:1:0.01) to give 5 g (63%) of 4-(3-dimethylamino-propyl)-3,5-dimethyl-1H-pyrrole-2-carbaldehyde as a dark red oil.

Workup

  1. customThe final reaction mixture
  2. temperaturewas refluxed at 60° C. for 4 hours
  3. temperaturecooled with ice bath
  4. additionIce cube was added to the reaction mixture
  5. stirringThe reaction mixture was stirred at room temperature for 30 minutes
  6. extractionextracted with ethyl acetate
  7. washThe organic-layer was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated
  10. customto give crude product which
  11. customwas purified on a silica gel column
  12. washeluting with dichloromethane-methanol-ammonium hydroxide (9:1:0.01)

Sources & evidence

ORD record
ord-46a2920882444286ae2665e83c20c755
Source dataset
uspto-grants-2004_02
Patent number
US06689806B1

Reaction notes

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