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

HRID 2172955Notes

Reaction equation

HRID 2172955 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]=[CH:12][CH:13]=1)=[O:4].C(=O)([O-])[O-].[K+].[K+].[F:20][C:21]1[CH:26]=[CH:25][C:24](I)=[CH:23][CH:22]=1.CN[C@@H]1CCCC[C@H]1NC>O.C(OCC)(=O)C.[Cu](I)I>[CH3:1][O:2][C:3]([C:5]1[C:6]2[CH:7]=[N:8][N:9]([C:24]3[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=3)[C:10]=2[CH:11]=[CH:12][CH:13]=1)=[O:4]

Participants

8

Reactant 4

HCID 96054-FluoroiodobenzeneHCID 11430Potassium CarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 6623327methyl 1H-indazole-4-carboxylate

Product 1

HCID 581388911-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 1H-indazole-4-carboxylic acid methyl ester (5.0 g, 28 mmol), copper iodide (5.7 g, 3.0 mmol), potassium carbonate (4.15 g, 30.0 mmol) and 4-fluoroiodobenzene (3.47 g, 30.0 mmol) is charged in a sealed tube at room temperature. The tube is evacuated, back-filled with argon and dimethylformamide (20 mL) is added followed by rac-trans-N,N′-dimethylcyclohexane-1,2-diamine (0.93 g, 6.5 mmol). The solution is stirred at 120° C. for 3 hours, then cooled to room temperature and diluted with water (50 mL) and ethyl acetate (80 mL). The organic layer is separated, washed with brine (30 mL), and dried over sodium sulfate. The crude product is filtered, concentrated and purified by silica gel chromatography eluting with a gradient of 0-30% ethyl acetate in hexanes to afford 1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid methyl ester.

Workup

  1. additionis charged in a sealed tube at room temperature
  2. customThe tube is evacuated
  3. additionback-filled with argon and dimethylformamide (20 mL)
  4. additionis added
  5. temperaturecooled to room temperature
  6. customThe organic layer is separated
  7. washwashed with brine (30 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationThe crude product is filtered
  10. concentrationconcentrated
  11. custompurified by silica gel chromatography
  12. washeluting with a gradient of 0-30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-c28981978c324f9cbceb0698de507072
Source dataset
uspto-grants-2015_06
Patent number
US09056858B2

Reaction notes

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