Sodium Bicarbonate → 4-(5-Amino-3-tert-butyl-pyrazol-1-yl)phenol

HRID 75589Notes

Reaction equation

HRID 75589 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH2:18])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16]C)=[CH:12][CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].[Cl-].[Cl-].[Cl-].[Al+3].C([O-])(O)=O.[Na+]>C(Cl)Cl>[NH2:18][C:7]1[N:8]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)[N:9]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH:6]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 6451240Aluminum(III) Chloride2×HCID 111393953-(tert-Butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-amine

Product 1

HCID 595579504-(5-Amino-3-tert-butyl-pyrazol-1-yl)phenolYield 53%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Intermediate 13a (10.0 g, 40.8 mmol) was dissolved in DCM (80.0 mL), and aluminium trichloride (28.0 g, 204.0 mmol) was added portionwise. The reaction was heated to reflux for 4 h. Additional aluminium trichloride (28.0 g, 204.0 mmol) was added portionwise, and the reaction heated at reflux overnight. After cooling, the mixture was carefully added portionwise to saturated aqueous NaHCO3 (300 mL). The mixture was extracted with ethyl acetate (300 mL) and separated. The aqueous layer was filtered under vacuo and acidified with 1N HCl until pH=7. This aqueous layer was then re-extracted into ethyl acetate, and the organic extracts were dried (MgSO4) and evaporated in vacuo. Purification by FCC, using 0-40% EtOAc in DCM, gave the title compound (5.0 g, 21.6 mmol, 53%). LCMS (method 1): Rt 2.77 min, m/z 232/233 [MH+].

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 4 h
  3. temperaturethe reaction heated
  4. temperatureat reflux overnight
  5. temperatureAfter cooling
  6. extractionThe mixture was extracted with ethyl acetate (300 mL)
  7. customseparated
  8. filtrationThe aqueous layer was filtered under vacuo
  9. extractionThis aqueous layer was then re-extracted into ethyl acetate
  10. dry with materialthe organic extracts were dried (MgSO4)
  11. customevaporated in vacuo
  12. customPurification by FCC

Sources & evidence

ORD record
ord-43c6a462a993457ca1a56fb5600f7883
Source dataset
uspto-grants-2014_09
Patent number
US08835431B2

Reaction notes

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