4-Bromophenol → 4-Indazol-2-ylphenol

HRID 1892659Notes

Reaction equation

HRID 1892659 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[NH:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[N:10]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Cu]I.C1(C)C=CC=CC=1>[N:9]1[N:10]([C:2]2[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=2)[CH:11]=[C:12]2[C:17]=1[CH:16]=[CH:15][CH:14]=[CH:13]2

Participants

6

Reactant 3

HCID 78084-BromophenolHCID 92211H-IndazoleHCID 62657Potassium Phosphate, Tribasic

Product 1

HCID 114243544-Indazol-2-ylphenolYield 20%

Reagents, catalysts & solvents 2

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

Procedure

4-Bromophenol (2.00 g, 11.6 mmol) was combined with 1H-indazole (1.64 g, 13.9 mmol), copper (I) iodide (110 mg, 0.578 mmol), potassium phosphate (5.15 g, 24.3 mmol), trans-dimethylcyclohexane-1,2-diamine (0.365 mL, 2.31 mmol), and toluene (10 mL). The reaction was refluxed for 21 hours, then cooled to room temperature and partitioned between ethyl acetate and water/ammonium hydroxide. The organic layer was washed with 0.5 N HCl and brine, dried over magnesium sulfate, filtered and concentrated. Purification by column chromatography (0-40% ethyl acetate in heptane) gave 4-(2H-indazol-2-yl)phenol (0.479 g, 20%) as a tan solid. 1H NMR (400 MHz, (CD3)2SO, δ): 9.84 (s, 1H), 8.90 (s, 1H), 7.86 (d, J=8.8 Hz, 2H), 7.74 (d, J=8.4 Hz, 1H), 7.68 (d, J=8.8 Hz, 1H), 7.22-7.33 (m, 1H), 7.03-7.12 (m, 1H), 6.94 (d, J=8.8 Hz, 2H). MS (M+1): 211.2.

Workup

  1. temperatureThe reaction was refluxed for 21 hours
  2. custompartitioned between ethyl acetate and water/ammonium hydroxide
  3. washThe organic layer was washed with 0.5 N HCl and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by column chromatography (0-40% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-fd17cbb2fc524507b883975d9f36f558
Source dataset
uspto-grants-2013_08
Patent number
US08507533B2

Reaction notes

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