Potassium Carbonate → 5-Amino-3-tert-butyl-pyrazol-1-yl-phenol

HRID 1402313Notes

Reaction equation

HRID 1402313 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH2:10])[NH:8][N:9]=1)([CH3:4])([CH3:3])[CH3:2].I[C:12]1[CH:13]=[C:14]([OH:18])[CH:15]=[CH:16][CH:17]=1.CN[C@H]1CCCC[C@@H]1NC.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.[Cu]I>[NH2:10][C:7]1[N:8]([C:13]2[CH:12]=[CH:17][CH:16]=[CH:15][C:14]=2[OH:18])[N:9]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH:6]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 122723-IodophenolHCID 13822957(1S,2S)-(+)-N,N'-Dimethylcyclohexane-1,2-diamineHCID 178441179HCID 178441179, compound

Product 1

HCID 587052255-Amino-3-tert-butyl-pyrazol-1-yl-phenolYield 86%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Procedure

A mixture of 5-tert-butyl-2H-pyrazol-3-ylamine (1 g, 7.18 mmol), 3-iodophenol (1.74 g, 7.90 mmol), copper (I) iodide (68 mg, 0.36 mmol), (1S,2S)—N,N′-dimethyl cyclohexane-1,2-diamine (204 mg, 1.44 mmol) and potassium carbonate (2.08 g, 15.09 mmol) in toluene (8 mL) was de-gassed and flushed with argon (3×). The reaction mixture was then treated with microwave irradiation, at 150° C. for 1 h. The mixture was diluted with EtOAc (20 mL) and washed with water (20 mL). The aqueous layer was extracted with a further 20 mL EtOAc and the combined organic layers were washed with brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue obtained was purified by FCC, using 0-100% EtOAc in cyclohexane to afford the title compound as a brown gum (1.42 g, 86%). LCMS (Method 3): Rt 2.21 min, m/z 232 [MH+].

Workup

  1. customwas de-gassed
  2. customflushed with argon (3×)
  3. additionThe reaction mixture was then treated with microwave irradiation, at 150° C. for 1 h
  4. additionThe mixture was diluted with EtOAc (20 mL)
  5. washwashed with water (20 mL)
  6. extractionThe aqueous layer was extracted with a further 20 mL EtOAc
  7. washthe combined organic layers were washed with brine (20 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue obtained
  12. customwas purified by FCC

Sources & evidence

ORD record
ord-711bab92233b49df8cc77912a6fd6e59
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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