Ethyl Acetate → 3-(2-methyl-1-phenylpropan-2-yl)-1-(2-phenylpropan-2-yl)-1H-pyrazol-5(4H)-one

HRID 244939Notes

Reaction equation

HRID 244939 reaction equation
[C:1]1([C:7]([NH:10][NH:11]C(OC(C)(C)C)=O)([CH3:9])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH3:31][C:32]([CH3:48])([CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:33](=O)[CH2:34][C:35]([O:37]CC)=O.C(OCC)(=O)C>C(Cl)Cl.C(O)(=O)C>[CH3:48][C:32]([C:33]1[CH2:34][C:35](=[O:37])[N:10]([C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)([CH3:9])[CH3:8])[N:11]=1)([CH3:31])[CH2:41][C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 521998p-Toluenesulfonic acid monohydrateHCID 19606120tert-Butyl 2-(2-phenylpropan-2-yl)hydrazinecarboxylateHCID 86697460Ethyl 4,4-dimethyl-3-oxo-5-phenylpentanoate

Product 1

HCID 866974613-(2-methyl-1-phenylpropan-2-yl)-1-(2-phenylpropan-2-yl)-1H-pyrazol-5(4H)-oneYield 12.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 2-(2-phenylpropan-2-yl)hydrazinecarboxylate (250 mg, 1.00 mmol) was dissolved in methylene chloride (2 mL), mixed with p-toluenesulfonic acid monohydrate (0.40 g, 2.1 mmol) and stirred at room temperature for 16 hours. After the stirring, the reaction solution was washed with saturated aqueous sodium hydrogen carbonate to terminate the reaction and then separated. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in toluene (3.0 mL) and acetic acid (70 μL), and mixed with ethyl 4,4-dimethyl-3-oxo-5-phenylpentanoate (248 mg, 1.00 mmol) and stirred at 90° C. for 3 hours. After completion of the reaction, the reaction solution was cooled to room temperature and mixed with ethyl acetate. The resulting organic layer was washed with saturated aqueous sodium hydrogen carbonate and then with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by intermediate pressure silica gel column chromatography (silica gel 12 g, ethyl acetate:hexane=1:9 to 3:7) to give 42 mg of the desired product as a brown oil.

Workup

  1. washAfter the stirring, the reaction solution was washed with saturated aqueous sodium hydrogen carbonate
  2. customto terminate
  3. customthe reaction
  4. customseparated
  5. washThe organic layer was washed with saturated aqueous sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. dissolutionThe resulting residue was dissolved in toluene (3.0 mL)
  10. stirringstirred at 90° C. for 3 hours
  11. customAfter completion of the reaction
  12. temperaturethe reaction solution was cooled to room temperature
  13. washThe resulting organic layer was washed with saturated aqueous sodium hydrogen carbonate
  14. dry with materialwith saturated aqueous sodium chloride, dried over anhydrous sodium sulfate
  15. filtrationfiltered
  16. concentrationthe filtrate was concentrated under reduced pressure
  17. customThe resulting residue was purified by intermediate pressure silica gel column chromatography (silica gel 12 g, ethyl acetate:hexane=1:9 to 3:7)

Sources & evidence

ORD record
ord-d5c9427774cd4c51a6bb94080b3e1a4d
Source dataset
uspto-grants-2014_02
Patent number
US08658686B2

Reaction notes

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