Sulfuric Acid → Ethyl 2-(3-chloro-2-pyridinyl)-2,5-dihydro-5-oxo-1H-pyrazole-3-carboxylate

HRID 1445537Notes

Reaction equation

HRID 1445537 reaction equation
[CH3:1][CH2:2][O:3][C:4]([CH:6]1[N:11]([C:12]2[N:17]=[CH:16][CH:15]=[CH:14][C:13]=2[Cl:18])[NH:10][C:8](=[O:9])[CH2:7]1)=[O:5].S(=O)(=O)(O)O.S(OOS([O-])(=O)=O)([O-])(=O)=O.[K+].[K+]>C(#N)C>[Cl:18][C:13]1[C:12]([N:11]2[C:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])=[CH:7][C:8](=[O:9])[NH:10]2)=[N:17][CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 24412Potassium PersulfateHCID 22280352Ethyl 2-(3-Chloro-2-pyridinyl)-5-oxo-3-pyrazolidinecarboxylate

Product 1

HCID 21113391Ethyl 2-(3-chloro-2-pyridinyl)-2,5-dihydro-5-oxo-1H-pyrazole-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of ethyl 1-(3-chloro-2-pyridinyl)-3-pyrazolidinone-5-carboxylate (i.e. the product of Step A) (27 g, 100 mmol) stirred in dry acetonitrile (200 mL) was added sulfuric acid (20 g, 200 mmol) in one portion. The reaction mixture thinned to form a pale green, nearly clear solution before thickening again to form a pale yellow suspension. Potassium persulfate (33 g, 120 mmol) was added in one portion, and then the reaction mixture was heated at gentle reflux for 3.5 hours. After cooling using an ice bath, a precipitate of white solid was removed by filtration and discarded. Concentration of the acetonitrile mother liquor and then dilution with water (400 mL) was followed by extraction three times with ethyl ether (700 mL total). The ethyl ether phase was concentrated to a reduced volume (75 mL) from which precipitated an-off white solid (3.75 g), which was collected by filtration. The ether mother liquor was further concentrated to yield a second crop of an off-white precipitate (4.2 g), which was collected by filtration. Further precipitation of an off-white solid (4.5 g) from the aqueous phase yielded a combined total of 12.45 g of the title compound.

Workup

  1. customThe reaction mixture thinned to form a pale green, nearly clear solution
  2. customto form a pale yellow suspension
  3. temperaturethe reaction mixture was heated
  4. temperatureat gentle reflux for 3.5 hours
  5. temperatureAfter cooling
  6. customa precipitate of white solid was removed by filtration
  7. extractionConcentration of the acetonitrile mother liquor and then dilution with water (400 mL) was followed by extraction three times with ethyl ether (700 mL total)
  8. concentrationThe ethyl ether phase was concentrated to a reduced volume (75 mL) from which
  9. customprecipitated an-off white solid (3.75 g), which
  10. filtrationwas collected by filtration
  11. concentrationThe ether mother liquor was further concentrated

Sources & evidence

ORD record
ord-7a16e7b31bad44ecb2154a18c0c8c7c6
Source dataset
uspto-grants-2010_02
Patent number
US07666882B2

Reaction notes

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