4-Fluoroiodobenzene → 6-bromo-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid methyl ester

HRID 2382959Notes

Reaction equation

HRID 2382959 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]2[CH:7]=[N:8][NH:9][C:10]=2[CH:11]=[C:12]([Br:14])[CH:13]=1)=[O:4].C(=O)([O-])[O-].[K+].[K+].[F:21][C:22]1[CH:27]=[CH:26][C:25](I)=[CH:24][CH:23]=1.CN[C@@H]1CCCC[C@H]1NC>O.C(OCC)(=O)C.[Cu]I.CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[C:6]2[CH:7]=[N:8][N:9]([C:25]3[CH:26]=[CH:27][C:22]([F:21])=[CH:23][CH:24]=3)[C:10]=2[CH:11]=[C:12]([Br:14])[CH:13]=1)=[O:4]

Participants

9

Reactant 4

HCID 96054-FluoroiodobenzeneHCID 11430Potassium CarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 24728062methyl 6-bromo-1H-indazole-4-carboxylate

Product 1

HCID 581387736-bromo-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 6-bromo-4-indazolecarboxylic acid methyl ester (2.0 g, 7.8 mmol), copper(I) iodide (0.4 g, 0.2 mmol), potassium carbonate (1.2 g, 8.5 mmol) and 4-fluoroiodobenzene (1.8 g, 8.5 mmol) was charged in a sealed tube at room temperature. The tube was evacuated and back-filled with argon, and DMF (10 mL) and rac-trans-N,N′-dimethylcyclohexane-1,2-diamine (0.20 g, 1.4 mmol) was added. The solution was stirred at 120° C. for 3 hours, cooled to room temperature, and diluted with water (30 mL) and ethyl acetate (50 mL). The organic layer was separated, washed with brine (10 mL) and dried over sodium sulfate. The solvent was removed in vacuo. The residue was purified by silica gel chromatography eluting with a gradient of 0-30% ethyl acetate in hexanes to afford 6-bromo-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid methyl ester.

Workup

  1. additionwas charged in a sealed tube at room temperature
  2. customThe tube was evacuated
  3. additionwas added
  4. temperaturecooled to room temperature
  5. customThe organic layer was separated
  6. washwashed with brine (10 mL)
  7. dry with materialdried over sodium sulfate
  8. customThe solvent was removed in vacuo
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with a gradient of 0-30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-a6bec7a07dad483cb642199bc1f2d222
Source dataset
uspto-grants-2012_09
Patent number
US08263597B2

Reaction notes

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