Acetic Acid → Ethyl 2-(3-Chloro-2-pyridinyl)-5-oxo-3-pyrazolidinecarboxylate

HRID 516521

Reaktionsgleichung

Reaktionsgleichung von HRID 516521
[O-]CC.[Na+].[Cl:5][C:6]1[C:7](=[N:12][NH2:13])[NH:8][CH:9]=[CH:10][CH:11]=1.[C:14](OCC)(=[O:22])/[CH:15]=[CH:16]\[C:17]([O:19][CH2:20][CH3:21])=[O:18].C(O)(=O)C>O.C(O)C>[Cl:5][C:6]1[C:7]([N:12]2[CH:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:15][C:14](=[O:22])[NH:13]2)=[N:8][CH:9]=[CH:10][CH:11]=1

Komponenten

7

Edukt 4

HCID 176Acetic AcidHCID 2723922Sodium ethoxideHCID 5271566Diethyl MaleateHCID 178514363HCID 178514363, Verbindung

Produkt 1

HCID 22280352Ethyl 2-(3-Chloro-2-pyridinyl)-5-oxo-3-pyrazolidinecarboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
83 °C

Versuchsvorschrift

A 2-L four-necked flask equipped with a mechanical stirrer, thermometer, addition funnel, reflux condenser, and nitrogen inlet was charged with absolute ethanol (250 mL) and an ethanolic solution of sodium ethoxide (21%, 190 mL, 0.504 mol). The mixture was heated to reflux at about 83° C. It was then treated with 3-chloro-2(1H)-pyridinone hydrazone (68.0 g, 0.474 mol). The mixture was re-heated to reflux over a period of 5 minutes. The yellow slurry was then treated dropwise with diethyl maleate (88.0 mL, 0.544 mol) over a period of 5 minutes. The reflux rate increased markedly during the addition. By the end of the addition all of the starting material had dissolved. The resulting orange-red solution was held at reflux for 10 minutes. After being cooled to 65° C. the reaction mixture was treated with glacial acetic acid (50.0 mL, 0.873 mol). A precipitate formed. The mixture was diluted with water (650 mL), causing the precipitate to dissolve. The orange solution was cooled in an ice bath. Product began to precipitate at 28° C. The slurry was held at about 2° C. for 2 hours. The product was isolated via filtration, washed with aqueous ethanol (40%, 3×50 mL), and then air-dried on the filter for about 1 hour. The title product compound was obtained as a highly crystalline, light orange powder (70.3 g, 55% yield). No significant impurities were observed by 1H NMR.

Aufarbeitung

  1. customA 2-L four-necked flask equipped with a mechanical stirrer
  2. additionthermometer, addition funnel
  3. temperaturereflux condenser, and nitrogen inlet
  4. temperatureThe mixture was heated
  5. temperatureThe mixture was re-heated
  6. temperatureto reflux over a period of 5 minutes
  7. temperatureThe reflux rate increased markedly during the addition
  8. additionBy the end of the addition all of the starting material
  9. dissolutionhad dissolved
  10. temperatureat reflux for 10 minutes
  11. temperatureAfter being cooled to 65° C. the reaction mixture
  12. customA precipitate formed
  13. dissolutionto dissolve
  14. temperatureThe orange solution was cooled in an ice bath
  15. customto precipitate at 28° C
  16. customThe product was isolated via filtration
  17. washwashed with aqueous ethanol (40%, 3×50 mL)
  18. customair-dried on the
  19. filtrationfilter for about 1 hour

Quellen und Nachweise

ORD-Eintrag
ord-5eaa0b660cab4685a38736ca315409f8
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09113630B2

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