Acetic Acid → 3-tert-Butyl-1-(2-methylphenyl)-1H-pyrazol-5-amine

HRID 2109926Notes

Reaction equation

HRID 2109926 reaction equation
[CH3:1][C:2]([CH3:9])([CH3:8])[C:3](=O)[CH2:4][C:5]#[N:6].Cl.[CH3:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[NH:18][NH2:19].C(O)(=O)C.C(=O)(O)[O-].[Na+]>C(O)C.CCCCCC>[C:2]([C:3]1[CH:4]=[C:5]([NH2:6])[N:18]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[CH3:11])[N:19]=1)([CH3:9])([CH3:8])[CH3:1]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 71554o-Tolylhydrazinium(1+) chlorideHCID 108871Pentanenitrile, 4,4-dimethyl-3-oxo-HCID 516892Sodium Bicarbonate

Product 1

HCID 7706433-tert-Butyl-1-(2-methylphenyl)-1H-pyrazol-5-amineYield 93%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8058HexaneSolvent

Procedure

4,4-Dimethyl-3-oxopentanenitrile (36.7 g, 0.29 mol), (2-methylphenyl)hydrazine hydrochloride (47.7 g, 0.29 mol), and glacial acetic acid (7.03 g, 6.7 mL, 0.12 mol) were dissolved in abs ethanol (585 mL) and heated under reflux for 18 h. After removal of the solvent under reduced pressure, EtOAc and water (500 mL each) were added, then sodium bicarbonate (42 g, 0.50 mol) was carefully added. After addition of hexane (500 mL), the organic phase was separated, washed with brine (500 mL), and dried over Na2SO4. The mixture was then filtered through a pad of silica gel (500 g) on a sintered glass funnel. The pad was eluted with hexanes/EtOAc (1:1, v/v), and the filtrate was concentrated under reduced pressure. The resulting solid was triturated with hexanes/EtOAc (9:1, v/v), filtered, washed and dried in vacuo to afford the product as a colorless solid (61.5 g, 93%). 1H NMR (400 MHz, CD2Cl2) δ 1.29 (s, 9H), 2.12 (s, 3H), 3.56 (br, 2H), 5.48 (s, 1H), 7.28 (m, 2H), 7.31 (m, 2H).

Workup

  1. temperatureheated
  2. temperatureunder reflux for 18 h
  3. customAfter removal of the solvent under reduced pressure, EtOAc and water (500 mL each)
  4. additionwere added
  5. customthe organic phase was separated
  6. washwashed with brine (500 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationThe mixture was then filtered through a pad of silica gel (500 g) on a sintered glass funnel
  9. washThe pad was eluted with hexanes/EtOAc (1:1
  10. concentrationv/v), and the filtrate was concentrated under reduced pressure
  11. customThe resulting solid was triturated with hexanes/EtOAc (9:1
  12. filtrationv/v), filtered
  13. washwashed
  14. customdried in vacuo

Sources & evidence

ORD record
ord-f2c886862b2942a6b5da7fbd2b413d20
Source dataset
uspto-grants-2009_04
Patent number
US07517878B2

Reaction notes

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