Diethyl Oxalate → ethyl 5-(3-benzenesulfonylpropyl)-1-butyl-1H-pyrazole-3-carboxylate

HRID 1360546Notes

Reaction equation

HRID 1360546 reaction equation
CC(C)([O-])C.[Na+].[C:7]1([S:13]([CH2:16][CH2:17][CH2:18][C:19](=O)[CH3:20])(=[O:15])=[O:14])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C:22]([O:29][CH2:30][CH3:31])(=[O:28])[C:23](OCC)=O.C([O-])(=O)C.[K+].C(O)(=O)C(O)=O.[CH2:43]([NH:47][NH2:48])[CH2:44][CH2:45][CH3:46]>C(O)C.C(O)(=O)C>[C:7]1([S:13]([CH2:16][CH2:17][CH2:18][C:19]2[N:47]([CH2:43][CH2:44][CH2:45][CH3:46])[N:48]=[C:23]([C:22]([O:29][CH2:30][CH3:31])=[O:28])[CH:20]=2)(=[O:15])=[O:14])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

8

Reactant 5

HCID 7268Diethyl OxalateHCID 162021Butylhydrazine oxalateHCID 3456215-Benzenesulfonylpentan-2-oneHCID 517044Potassium AcetateHCID 23676156Sodium t-butoxide

Product 1

HCID 66959126ethyl 5-(3-benzenesulfonylpropyl)-1-butyl-1H-pyrazole-3-carboxylateYield 47.4%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 702EthanolSolvent2×

Conditions

Temperature
0 °C

Procedure

Sodium tert-butoxide (15.4 g, 160 mmol) was combined with ethanol (53 mL) and allowed to stir for 30 minutes. 5-Benzenesulfonylpentan-2-one (16.8 g, 74.2 mmol) and diethyl oxalate (10.1 mL, 74.2 mmol) were added to the reaction mixture in 20 mL of ethanol via an addition funnel. The reaction was maintained for 1 hour and the solution changed in color from orange to red. Potassium acetate (10.9 g, 111 mmol) was added to the reaction mixture, followed by addition of acetic acid (37 mL, 2M). The reaction mixture was then cooled to 0° C. and butyl hydrazine oxalate (13.2 g, 74.2 mmol) was added. The resultant slurry was stirred for 2 hours and turned yellow. The reaction mixture was concentrated under reduced pressure, diluted with water, and the pH of the mixture was adjusted to 11 by addition of sodium carbonate. The reaction mixture was extracted with chloroform while adding additional water to minimize elusion formation. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to afford a red oil. The material was purified by column chromatography on silica gel (eluting with hexane:ethyl acetate in a gradient from 3:1 to 1:1) to yield 13.3 g of ethyl 5-(3-benzenesulfonylpropyl)-1-butyl-1H-pyrazole-3-carboxylate as an orange oil.

Workup

  1. temperatureThe reaction was maintained for 1 hour
  2. stirringThe resultant slurry was stirred for 2 hours
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additiondiluted with water
  5. additionthe pH of the mixture was adjusted to 11 by addition of sodium carbonate
  6. extractionThe reaction mixture was extracted with chloroform
  7. additionwhile adding additional water
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customto afford a red oil
  13. customThe material was purified by column chromatography on silica gel (
  14. washeluting with hexane

Sources & evidence

ORD record
ord-e3753539e9a74e68a73f4d27b900e7dd
Source dataset
uspto-grants-2011_02
Patent number
US07879849B2

Reaction notes

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