Acetic Acid → 3-tert-butyl-1-(4-nitrophenyl)-1H-pyrazol-5-amine

HRID 1174830Notes

Reaction equation

HRID 1174830 reaction equation
[CH3:1][C:2]([CH3:9])([CH3:8])[C:3](=O)[CH2:4][C:5]#[N:6].[N+:10]([C:13]1[CH:18]=[CH:17][C:16]([NH:19][NH2:20])=[CH:15][CH:14]=1)([O-:12])=[O:11].C(O)(=O)C>CCO>[C:2]([C:3]1[CH:4]=[C:5]([NH2:6])[N:19]([C:16]2[CH:15]=[CH:14][C:13]([N+:10]([O-:12])=[O:11])=[CH:18][CH:17]=2)[N:20]=1)([CH3:9])([CH3:8])[CH3:1]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 108871Pentanenitrile, 4,4-dimethyl-3-oxo-HCID 3310889(4-Nitrophenyl)hydrazine

Product 1

HCID 13023603-tert-butyl-1-(4-nitrophenyl)-1H-pyrazol-5-amineYield 85%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 4,4-dimethyl-3-oxopentanenitrile (20.4 g, 163 mmol) and 4-nitrophenylhydrazine (25.0 g, 163 mmol) in anhydrous EtOH (300 mL) was added acetic acid (3.4 mL, 60 mL) dropwise. The reaction was stirred at reflux under N2 for 18 h. The reaction mixture was cooled to room temperature and concentrated at reduced pressure. The residue was partitioned between EtOAc (500 mL) and aqueous saturated NaHCO3 solution (300 mL). The organic layer was washed with water and brine, dried over Na2SO4, and concentrated at reduced pressure. The crude residue was purified by MPLC (eluting with 80:20 hexanes/EtOAc) to give 36.0 g (85%) of the desired product. 1H-NMR (DMSO-d6) δ 8.28 (d, J=6.9 Hz, 2H), 7.93 (d, J=6.9 Hz, 2H), 5.55 (s, 2H), 5.46 (s, 1H), 1.20 (s, 9H); MS LC-MS [M+H]+=261, RT=2.74 min.

Workup

  1. temperatureat reflux under N2 for 18 h
  2. concentrationconcentrated at reduced pressure
  3. customThe residue was partitioned between EtOAc (500 mL) and aqueous saturated NaHCO3 solution (300 mL)
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated at reduced pressure
  7. customThe crude residue was purified by MPLC (eluting with 80:20 hexanes/EtOAc)

Sources & evidence

ORD record
ord-89ae59e825404982bce1de97966f1b8a
Source dataset
uspto-grants-2010_11
Patent number
US07838524B2

Reaction notes

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