Acetic Acid → Ethyl 3-tert-butyl-1H-pyrazole-5-carboxylate

HRID 1930370Notes

Reaction equation

HRID 1930370 reaction equation
[Na].[CH3:2][C:3]([CH3:8])([CH3:7])[C:4](=O)[CH3:5].[CH2:9]([O:11][C:12](=[O:18])[C:13](OCC)=O)[CH3:10].C(O)(=O)C.O.[NH2:24][NH2:25]>>[C:3]([C:4]1[CH:5]=[C:13]([C:12]([O:11][CH2:9][CH3:10])=[O:18])[NH:25][N:24]=1)([CH3:8])([CH3:7])[CH3:2]

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 6416PinacoloneHCID 7268Diethyl OxalateHCID 24654Hydrazine hydrate (1:1)HCID 5360545Sodium

Product 1

HCID 2743509Ethyl 3-tert-butyl-1H-pyrazole-5-carboxylateYield 50%

Procedure

Sodium metal (13.8 g, 0.5 mol) was added portionwise to ice-cold anhydrous EtOH (700 mL). After complete dissolution of the Na, a mixture of 3,3-dimethylbutan-2-one (50 g, 0.5 mol) and oxalic acid diethyl ester (77 ml, 0.5 mol) was added drop-wise. The reaction mixture was stirred in ice-salt bath and until TLC indicated completion of the reaction. Acetic acid (38.1 ml, 0.5 mol) was added and the mixture was stirred at RT for 30 min. The reaction mixture was cooled in an ice-salt bath and treated with hydrazine hydrate (29.4 g, 0.5 mol). After complete addition, the mixture was warmed to RT and stirred until judged complete by TLC. The reaction mixture was concentrated under reduced pressure and re-dissolved in EtOAc. The EtOAc solution was washed with NaHCO3, brine and water, dried (MgSO4) and concentrated in vacuo. The resultant solid was washed with cold petroleum ether to give ethyl 3-tert-butyl-1 H-pyrazole-5-carboxylate (49 g, 50% yield over two steps) as a white solid. 1H NMR (400 MHz, CDCl3): δ 6.65 (s, 1 H), 4.38 (q, J=6.8 Hz, 2 H), 1.39 (t, J=6.8 Hz, 3 H), 1.35 (s, 1H); MS (ESI) m/z: 197.2 (M+H+).

Workup

  1. additionwas added drop-wise
  2. customcompletion of the reaction
  3. temperatureThe reaction mixture was cooled in an ice-salt bath
  4. additionAfter complete addition
  5. temperaturethe mixture was warmed to RT
  6. stirringstirred
  7. concentrationThe reaction mixture was concentrated under reduced pressure
  8. dissolutionre-dissolved in EtOAc
  9. washThe EtOAc solution was washed with NaHCO3, brine and water
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated in vacuo
  12. washThe resultant solid was washed with cold petroleum ether

Sources & evidence

ORD record
ord-3941af7cd20c41859dca58e768b42063
Source dataset
uspto-grants-2012_05
Patent number
US08188113B2

Reaction notes

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