Ethyl Acetate → 4-(5-Amino-3-tert-butyl-pyrazol-1-yl)phenol

HRID 221863Notes

Reaction equation

HRID 221863 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(OCC)(=O)C>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 8857Ethyl AcetateHCID 6451240Aluminum(III) ChlorideHCID 111393953-(tert-Butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-amine

Product 1

HCID 595579504-(5-Amino-3-tert-butyl-pyrazol-1-yl)phenolYield 54.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 5-tert-butyl-2-(4-methoxyphenyl)-2H-pyrazol-3-ylamine (5.3 g, 21.6 mmol) in anhydrous DCM (43.2 mL) was added aluminum trichloride (14.4 g, 108.0 mmol, 5.0 eq) proportion wise, and the reaction was stirred at reflux for 18 h. The cooled reaction was poured into ethyl acetate, and the organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated at reduced pressure. Crystallization from DCM/ether afforded the title compound (2.71 g, 54%) as a white solid. 1H-NMR (DMSO-d6) δ 9.47 (s, 1H), 7.21 (d, J=9.0 Hz, 2H), 6.75 (d, J=8.7 Hz, 2H), 5.25 (s, 1H), 4.91 (broad s, 2H), 1.13 (s, 9H); MS LC-MS [M+H]+=232, RT=1.13 min; TLC (35% EtOAc/hex), Rf=0.13.

Workup

  1. temperatureat reflux for 18 h
  2. customThe cooled reaction
  3. washthe organic layer was washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated at reduced pressure
  7. customCrystallization from DCM/ether

Sources & evidence

ORD record
ord-68b32bed981f40f3b9269ed5fa43ecdd
Source dataset
uspto-grants-2012_06
Patent number
US08207166B2

Reaction notes

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