Hydrochloric Acid → Ethyl 1-ethyl-4-methyl-1H-pyrazole-3-carboxylate

HRID 1874369Notes

Reaction equation

HRID 1874369 reaction equation
Cl[C:2](Cl)(Cl)[C:3](Cl)=[O:4].C([O:10]C=CC)C.Cl.[CH2:15]([NH:17]N)[CH3:16].[N:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C(O)C.C(OCC)C>[CH2:24]([N:19]1[CH:20]=[C:21]([CH3:22])[C:15]([C:16]([O:4][CH2:3][CH3:2])=[O:10])=[N:17]1)[CH3:23]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 6420Trichloroacetyl chlorideHCID 13570Ethyl 1-propenyl etherHCID 29062Ethylhydrazine

Product 1

HCID 57749287Ethyl 1-ethyl-4-methyl-1H-pyrazole-3-carboxylateYield 18%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Procedure

To trichloroacetyl chloride (29.4 mL, 262 mmol) was added dropwise with stirring under ice-cooling a solution of 1-ethoxyprop-1-en (25.0 g, 290 mmol) in pyridine (21.2 mL) over 30 min, diethyl ether (100 mL) was added, and the mixture was stirred at room temperature for 17 hr. 0.2N Hydrochloric acid (200 mL) was added to the reaction mixture, and the organic layer was separated, washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was dissolved in ethanol (130 mL). A solution of ethylhydrazine (17.4 g, 290 mmol) in ethanol (130 mL) was added over 10 min, and the mixture was stirred at 80° C. for 2 hr. The reaction mixture was concentrated under reduced pressure, and ethyl acetate and saturated aqueous sodium hydrogen carbonate solution were added to the residue. The organic layer was separated, washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (silica gel, hexane/ethyl acetate=95/5→50/50) to give the title compound (8.82 g, 18%) as a colorless oil.

Workup

  1. stirringthe mixture was stirred at room temperature for 17 hr
  2. customthe organic layer was separated
  3. washwashed with water and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltrated
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. dissolutionthe residue was dissolved in ethanol (130 mL)
  8. stirringthe mixture was stirred at 80° C. for 2 hr
  9. concentrationThe reaction mixture was concentrated under reduced pressure, and ethyl acetate and saturated aqueous sodium hydrogen carbonate solution
  10. additionwere added to the residue
  11. customThe organic layer was separated
  12. washwashed with water and saturated brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. filtrationfiltrated
  15. concentrationThe filtrate was concentrated under reduced pressure
  16. customthe residue was purified by column chromatography (silica gel, hexane/ethyl acetate=95/5→50/50)

Sources & evidence

ORD record
ord-cc5604101c9e4ca281bef55610b240cc
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Reaction notes

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