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

HRID 2382931Notes

Reaction equation

HRID 2382931 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>[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 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 1H-indazole-4-carboxylic acid methyl ester (5.0 g, 28 mmol), copper(I) iodide (5.7 g, 3.0 mmol), potassium carbonate (4.15 g, 30.0 mmol) and 4-fluoroiodobenzene (3.47 g, 30.0 mmol) was charged in a sealed tube at room temperature. The tube was evacuated, back-filled with argon and dimethylformamide (20 mL) was added followed by rac-trans-N,N′-dimethylcyclohexane-1,2-diamine (0.93 g, 6.5 mmol). The solution was stirred at 120° C. for 3 hours. The solution was cooled to room temperature and diluted with water (50 mL) and ethyl acetate (80 mL). The organic layer was separated, washed with brine (30 mL), and dried over sodium sulfate. The crude product was 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. additionwas charged in a sealed tube at room temperature
  2. customThe tube was evacuated
  3. additionback-filled with argon and dimethylformamide (20 mL)
  4. additionwas added
  5. temperatureThe solution was cooled to room temperature
  6. customThe organic layer was separated
  7. washwashed with brine (30 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationThe crude product was 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-85a799ebfdfa48f28af5499709c22c9f
Source dataset
uspto-grants-2012_09
Patent number
US08263597B2

Reaction notes

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