4-Bromophenol → 4-(6-Fluoro-indazol-2-yl)-phenol

HRID 1520873Notes

Reaction equation

HRID 1520873 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:18]=[C:17]2[C:13]([CH:14]=[N:15][NH:16]2)=[CH:12][CH:11]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CNCCNC>[Cu]I.C1(C)C=CC=CC=1>[F:9][C:10]1[CH:11]=[CH:12][C:13]2[C:17]([CH:18]=1)=[N:16][N:15]([C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1)[CH:14]=2

Participants

7

Reactant 4

HCID 78084-BromophenolHCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 178423506-Fluoro-1H-indazole

Product 1

HCID 681576534-(6-Fluoro-indazol-2-yl)-phenolYield 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 6-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-(6-fluoro-indazol-2-yl)-phenol (0.129 g, 8%) as a tan solid. The other regioisomer was also observed but was separated by chromatography. 1H NMR (400 MHz, DMSO-d6, δ): 9.86 (s, 1H) 8.96 (s, 1H) 7.75-7.91 (m, 3H) 7.41 (d, J=10.6 Hz, 1H) 6.99 (td, J=9.3, 2.2 Hz, 1H) 6.93 (d, J=8.8 Hz, 2H); 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-39ac2683be194fb692cc6d4a5f14f037
Source dataset
uspto-grants-2015_07
Patent number
US09073871B2

Reaction notes

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