Trityl chloride → 5-Bromo-1-trityl-1H-indazole-3-carboxylic Acid

HRID 34094Notes

Reaction equation

HRID 34094 reaction equation
C([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([Br:15])[CH:13]=2)[NH:8][N:7]=1)=[O:5])C.[H-].[Na+].[C:18](Cl)([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[Cl-].[NH4+]>CN(C)C=O>[Br:15][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:18]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)([C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)[N:7]=[C:6]2[C:4]([OH:3])=[O:5]

Participants

6

Reactant 4

HCID 6456Trityl chlorideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 12689364ethyl 5-bromo-2H-indazole-3-carboxylate

Product 1

HCID 230701175-Bromo-1-trityl-1H-indazole-3-carboxylic AcidYield 83.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2.19 g of 5-bromo-1H-indazole-3-carboxylic acid ethyl ester was dissolved in 40 mL of dimethylformamide, added with 391 mg of 60% sodium hydride (oil-based) and 2.38 g of trityl chloride, and stirred at room temperature for 1 hour. After adding a saturated aqueous ammonium chloride, the reaction solution was extracted with ethyl acetate, and the resultant organic layer was washed with saturated brine, dried over magnesium sulfate, and the solvent was evaporated. The resultant residue was dissolved in a solution of 20 mL of ethanol, 20 mL of tetrahydrofuran and 15 mL of 5N sodium hydroxide aqueous, and stirred at 60° C. for 2 hours. After allowing to cool to room temperature, the reaction solution was neutralized by adding 1N hydrochloric acid, extracted with a mixed solvent of ethyl acetate:tetrahydrofuran=1:1, and the resultant organic layer was washed with saturated brine and dried over magnesium sulfate. After evaporated the solvent, the generated crystals were washed with diethyl ether and filtered to afford 3.3 g of the title compound as pale yellow crystals.

Workup

  1. extractionthe reaction solution was extracted with ethyl acetate
  2. washthe resultant organic layer was washed with saturated brine
  3. dry with materialdried over magnesium sulfate
  4. customthe solvent was evaporated
  5. dissolutionThe resultant residue was dissolved in a solution of 20 mL of ethanol, 20 mL of tetrahydrofuran and 15 mL of 5N sodium hydroxide aqueous
  6. stirringstirred at 60° C. for 2 hours
  7. temperatureto cool to room temperature
  8. additionby adding 1N hydrochloric acid
  9. extractionextracted with a mixed solvent of ethyl acetate
  10. washtetrahydrofuran=1:1, and the resultant organic layer was washed with saturated brine
  11. dry with materialdried over magnesium sulfate
  12. customAfter evaporated the solvent
  13. washthe generated crystals were washed with diethyl ether
  14. filtrationfiltered

Sources & evidence

ORD record
ord-baef361087334cffb56269ad1a6b817d
Source dataset
uspto-grants-2008_09
Patent number
US07429609B2

Reaction notes

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