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

HRID 61953

Reaction equation

HRID 61953 reaction equation
[Cl:1][C:2]1[C:3]([N:8]2[CH:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:11][C:10](=[O:18])[NH:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.S(=O)(=O)(O)O.S(OOS([O-])(=O)=O)([O-])(=O)=O.[K+].[K+]>C(#N)C>[Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][C:10](=[O:18])[NH:9]2)=[N:4][CH:5]=[CH:6][CH:7]=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-carboxylateYield 15.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolidinecarboxylate (i.e. product of Example 8, 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. The filtrate was diluted with water (400 mL) and then extracted three times with ethyl ether (700 mL total). Concentration of the combined ether extracts to a reduced volume (75 mL) caused precipitation of 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 also collected by filtration. An off-white solid also precipitated from the aqueous phase; this solid (4.5 g) was collected by filtration to provide 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. additionThe filtrate was diluted with water (400 mL)
  8. extractionextracted three times with ethyl ether (700 mL total)
  9. customprecipitation of 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-a7e940b781464c998f385d3ac83e1718
Source dataset
uspto-grants-2016_09
Patent number
US09445593B1

Linked notes

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