Carbon Dioxide → Ethyl 2,4-dimethyl-5-(ethoxycarbonyl)-3-pyrrolepropionate

HRID 1761137Notes

Reaction equation

HRID 1761137 reaction equation
[C:1]([CH:4](C)[C:5](=O)[CH2:6][CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])(=O)C.Cl.[NH2:16][CH:17]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:18](OCC)=O.[C:28]([O-])(=O)C.[Na+].C(=O)=O>C(O)(=O)C>[CH2:26]([O:25][C:23]([C:17]1[NH:16][C:4]([CH3:1])=[C:5]([CH2:6][CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:18]=1[CH3:28])=[O:24])[CH3:27]

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 517045Sodium AcetateHCID 3084143Propanedioic acid, 2-amino-, 1,3-diethyl ester, hydrochloride (1:1)HCID 13545064Ethyl 5-acetyl-4-oxohexanoate

Product 1

HCID 291761Ethyl 2,4-dimethyl-5-(ethoxycarbonyl)-3-pyrrolepropionateYield 68.6%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
99 °C

Procedure

To a 5 L three-neck flask, equipped with a thermometer and a mechanical stirrer and heated on a steam bath, was added 350 g of ethyl 5-acetyl-4-oxohexanoate, 329 g of diethyl aminomalonate hydrochloride, 133 g of sodium acetate, and 1.2 L of acetic acid. The mixture was heated to 99° C. over 37 minutes. By 62° C., carbon dioxide evolution was already rapid. After a total of 35 minutes at 99° C., gas evolution had greatly slowed. After another hour, the mixture was cooled, the sodium chloride removed by vacuum filtration, and the solvent evaporated. The residue was mixed with 1 L of cold water. The precipitate was collected by vacuum filtration, washed with 400 mL of water, and dissolved in 1 L of hot 95% ethanol. The solution was treated with 20 g of Darco G-60, hot-filtered, and cooled to room temperature. The crystalline solid was collected by vacuum filtration, washed twice on the filter with 200 mL of 50% ethanol each time, and dried under vacuum at 70° C. to give 285 g (64% yield) of 2-ethoxycarbonyl-4-(2-ethoxycarbonylethyl)-3,5-dimethylpyrrole. The filtrate was refrigerated overnight to give another 53.1 g (11.9% yield) of product, for a total yield of 75.9%.

Workup

  1. customTo a 5 L three-neck flask, equipped with a thermometer and a mechanical stirrer
  2. temperatureheated on a steam bath
  3. customBy 62° C.
  4. customAfter a total of 35 minutes
  5. customat 99° C.
  6. waitAfter another hour
  7. temperaturethe mixture was cooled
  8. customthe sodium chloride removed by vacuum filtration
  9. customthe solvent evaporated
  10. additionThe residue was mixed with 1 L of cold water
  11. filtrationThe precipitate was collected by vacuum filtration
  12. washwashed with 400 mL of water
  13. dissolutiondissolved in 1 L of hot 95% ethanol
  14. additionThe solution was treated with 20 g of Darco G-60
  15. filtrationhot-filtered
  16. temperaturecooled to room temperature
  17. filtrationThe crystalline solid was collected by vacuum filtration
  18. washwashed twice on the
  19. filtrationfilter with 200 mL of 50% ethanol each time
  20. customdried under vacuum at 70° C.

Sources & evidence

ORD record
ord-eff38c3df9de47a8994c551c88cb7ba1
Source dataset
uspto-grants-2005_01
Patent number
US06846839B1

Reaction notes

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