4-Bromophenol → 4-(5-Fluoro-indazol-2-yl)-phenol

HRID 537498Notes

Reaction equation

HRID 537498 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[F:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[NH:15][N:14]=[CH:13]2.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CNCCNC>[Cu]I.C1(C)C=CC=CC=1>[F:9][C:10]1[CH:18]=[CH:17][C:16]2[C:12](=[CH:13][N:14]([C:2]3[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=3)[N:15]=2)[CH:11]=1

Participants

7

Reactant 4

HCID 78084-BromophenolHCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 178424865-Fluoro-1H-indazole

Product 1

HCID 681576274-(5-Fluoro-indazol-2-yl)-phenolYield 6.8%

Reagents, catalysts & solvents 2

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

Procedure

4-bromophenol (1.27 g, 7.35 mmol) was combined with 5-fluoro-1H-indazole (1.000 g, 7.35 mmol), CuI (69.9 mg, 0.367 mmol), K3PO4 (3.282 g, 15.4 mmol), toluene (15 mL), and dimethylethylenediamine (0.158 mL, 1.47 mmol). This was refluxed as a mixture for 3 d. The reaction was cooled and partitioned between ethyl acetate and sat. NH4Cl. The aqueous was extracted with ethyl acetate and the combined organics were dried over MgSO4. Purification by silica gel flash chromatography (ethyl acetate in heptane) gave 4-(5-fluoro-indazol-2-yl)-phenol (0.114 g) impure with the indazole starting material. Used as is. The other regioisomer was also observed but was separated by chromatography. MS (M+1): 229.2.

Workup

  1. temperatureThis was refluxed as a mixture for 3 d
  2. temperatureThe reaction was cooled
  3. custompartitioned between ethyl acetate and sat. NH4Cl
  4. extractionThe aqueous was extracted with ethyl acetate
  5. dry with materialthe combined organics were dried over MgSO4
  6. customPurification by silica gel flash chromatography (ethyl acetate in heptane)

Sources & evidence

ORD record
ord-e922a497d80f4a278ac32b88b4e124c7
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

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