Water → Ethyl 1-ethyl-5-methyl-1H-pyrazole-3-carboxylate

HRID 1825345Notes

Reaction equation

HRID 1825345 reaction equation
C(O)(=O)C(O)=O.[CH2:7]([NH:9][NH2:10])[CH3:8].O=[C:12]([CH2:18][C:19](=O)[CH3:20])[C:13]([O:15][CH2:16][CH3:17])=[O:14].O.C([O-])([O-])=O.[K+].[K+]>C(O)(=O)C.C(OCC)(=O)C>[CH2:7]([N:9]1[C:19]([CH3:20])=[CH:18][C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[N:10]1)[CH3:8]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 69208Ethyl 2,4-dioxovalerateHCID 96181Hydrazine, ethyl-, ethanedioate (1:1)2×

Product 1

HCID 16394811Ethyl 1-ethyl-5-methyl-1H-pyrazole-3-carboxylate

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-Ethylhydrazine oxalate (12 g) in glacial acetic acid (100 ml) was cooled in an ice-bath and treated with ethyl 2,4-dioxovalerate (11.24 ml). After addition was complete the mixture was stirred at room temperature; after ca. 45 min the mixture was warmed to dissolve insoluble ethylhydrazine oxalate. The mixture was stirred for a further 2 h and then poured into water (ca. 300 ml)/ethyl acetate (ca. 700 ml) and solid K2CO3 was carefully added, with stirring, until the pH was neutral. After separation the aqueous layer was re-extracted with ethyl acetate. The combined ethyl acetate extracts were dried (MgSO4), and the solvents removed to leave an oil. Chromatography on silica gel, loading in CH2Cl2/hexane and eluting with a gradient elution of ethyl acetate/hexane mixtures (from 2:8 to 1:1) gave ethyl 1-ethyl-5-methylpyrazole-3-carboxylate as an oil (13.2 g); υmax (CH2Cl2) 1717, 1446, 1389, and 1219 cm−1; δ(CDCl3) 1.38 (3H, t, J 7.2 Hz), 1.42 (3H, t, J 7.3 Hz), 2.30 (3H, s), 4.17 (2H, q, J 7.3 Hz), 4.38 (2H, q, J 7.1 Hz), 6.55 (1H, s); (Found m/z 182.1055. C9H14N2O2 requires m/z 182.1055).

Workup

  1. additionAfter addition
  2. temperatureafter ca. 45 min the mixture was warmed
  3. stirringThe mixture was stirred for a further 2 h
  4. additionwas carefully added
  5. stirringwith stirring, until the pH
  6. customAfter separation the aqueous layer
  7. extractionwas re-extracted with ethyl acetate
  8. dry with materialThe combined ethyl acetate extracts were dried (MgSO4)
  9. customthe solvents removed
  10. customto leave an oil
  11. washChromatography on silica gel, loading in CH2Cl2/hexane and eluting with a gradient elution of ethyl acetate/hexane mixtures (from 2:8 to 1:1)

Sources & evidence

ORD record
ord-38dbc6f22e1949519a0d1754cf554345
Source dataset
uspto-grants-2006_05
Patent number
US07045619B2

Reaction notes

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