Dimethylformamide → ethyl 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylate

HRID 1888973Notes

Reaction equation

HRID 1888973 reaction equation
P(Cl)(Cl)(Cl)=O.[CH2:6]([O:8][C:9]([C:11]1[C:15]([CH3:16])=[CH:14][NH:13][C:12]=1[CH3:17])=[O:10])[CH3:7].CN(C)[CH:20]=[O:21]>>[CH2:6]([O:8][C:9]([C:11]1[C:15]([CH3:16])=[C:14]([CH:20]=[O:21])[NH:13][C:12]=1[CH3:17])=[O:10])[CH3:7]

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 24813Phosphorus oxychlorideHCID 137481Ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate

Product 1

HCID 137485ethyl 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylate

Conditions

Temperature
0 °C

Procedure

Into a 5-L four necked round-bottomed flask equipped with a mechanical stirrer, a thermometer pocket, addition funnel, air condenser and a nitrogen bubbler was charged dimethyl formamide (1.05 L). The solvent was cooled to 0° C. To this chilled solvent, phosphorous oxychloride (0.434 L) was charged at below 5° C. After addition, the temperature of the reaction mixture was slowly brought to 25-30° C. Then a solution of 2,4-dimethyl-1H-pyrrole-3-carboxylic acid ethyl ester (III) (0.7 Kg; 4.2 mole) dissolved in dimethyl formamide (1.05 L) was added drop-wise into the flask at 25-30° C. After addition, the temperature of the reaction mixture was brought to 50° C. and maintained for 2-3 hours. The reaction was monitored by TLC. After maintenance, the reaction mixture was cooled to 25-30° C. and quenched in a carboy containing ice-water. The pH of the solution was then adjusted to 12-13 using aq. KOH solution. After pH adjustment, the solution was stirred at 25-30° C. and filtered and washed with water. The product was dried in a hot air oven at 60° C.

Workup

  1. additiona thermometer pocket, addition funnel, air condenser
  2. additionAfter addition
  3. customwas slowly brought to 25-30° C
  4. additionwas added drop-wise into the flask at 25-30° C
  5. additionAfter addition
  6. customwas brought to 50° C.
  7. temperaturemaintained for 2-3 hours
  8. temperatureAfter maintenance, the reaction mixture was cooled to 25-30° C.
  9. customquenched in a carboy
  10. additioncontaining ice-water
  11. filtrationfiltered
  12. washwashed with water
  13. customThe product was dried in a hot air oven at 60° C.

Sources & evidence

ORD record
ord-f0f8a400cee645bea1c088c853ffb6e9
Source dataset
uspto-grants-2013_08
Patent number
US08501962B2

Reaction notes

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