Acetic Acid → 6-Fluoro-3-[(E)-2-(naphthalen-2-yl)-vinyl]-1H-indazole-5-carboxylic Acid

HRID 34033Notes

Reaction equation

HRID 34033 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](/[CH:11]=[CH:12]/[C:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[CH:14]=3)=[N:7][NH:8]2)=[CH:4]C=1C#N.S(=O)(=O)(O)O.[C:30]([OH:33])(=[O:32])[CH3:31]>O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](/[CH:11]=[CH:12]/[C:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[CH:14]=3)=[N:7][NH:8]2)=[CH:4][C:31]=1[C:30]([OH:33])=[O:32]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 1118Sulfuric AcidHCID 59797156HCID 59797156, compound

Product 1

HCID 597971456-Fluoro-3-[(E)-2-(naphthalen-2-yl)-vinyl]-1H-indazole-5-carboxylic Acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

To a suspension of 588 mg of 6-fluoro-3-[(E)-2-(naphthalen-2-yl)-vinyl]-1H-indazole-5-carbonitrile in 3 mL of acetic acid and 1 mL of water was added 3 mL of concentrated sulfuric acid, and stirred at 110° C. for 1 hours. After allowing to cool, the reaction solution was added with ice, and extracted with a mixed solvent of 30 mL ethyl acetate/15 mL tetrahydrofuran. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the resultant crude product was dissolved in 6 mL of 1,4-dioxane, added with 6 mL of 4N lithium hydroxide, and stirred at 120° C. for 15 hours. The reaction solution was made acidic with 5N hydrochloric acid, and then extracted with a mixed solvent of 30 mL ethyl acetate/20 mL tetrahydrofuran. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated, to afford 477 mg of the title compound as ocher crystals.

Workup

  1. temperatureto cool
  2. additionthe reaction solution was added with ice
  3. extractionextracted with a mixed solvent of 30 mL ethyl acetate/15 mL tetrahydrofuran
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated
  7. dissolutionthe resultant crude product was dissolved in 6 mL of 1,4-dioxane
  8. additionadded with 6 mL of 4N lithium hydroxide
  9. stirringstirred at 120° C. for 15 hours
  10. extractionextracted with a mixed solvent of 30 mL ethyl acetate/20 mL tetrahydrofuran
  11. washThe organic layer was washed successively with water and saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customThe solvent was evaporated

Sources & evidence

ORD record
ord-682045e9fd974f33817666bd20b34f94
Source dataset
uspto-grants-2008_09
Patent number
US07429609B2

Reaction notes

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