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

HRID 537499Notes

Reaction equation

HRID 537499 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, 7.3 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-222530c4fc3b4376aee40bda62da0db0
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

Loading…