Trityl chloride → 3-Bromo-4-fluoro-1-trityl-1H-indazole-5-carboxylic Acid Methyl Ester

HRID 503184Notes

Reaction equation

HRID 503184 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([F:15])=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][N:9]=[C:8]2[Br:14])=[O:4].[H-].[Na+].[C:18]1([C:24](Cl)([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(=O)([O-])O.[Na+]>O1CCCC1>[CH3:1][O:2][C:3]([C:5]1[C:6]([F:15])=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:24]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=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:9]=[C:8]2[Br:14])=[O:4]

Participants

6

Reactant 4

HCID 6456Trityl chlorideHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 178497388HCID 178497388, compound

Product 1

HCID 684205673-Bromo-4-fluoro-1-trityl-1H-indazole-5-carboxylic Acid Methyl EsterYield 30.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Under ice-cooling, to a solution of 2.99 g of 3-bromo-4-fluoro-1H-5-indazolecarboxylic acid methyl ester obtained in Production Example II-13-d in 30 ml tetrahydrofuran was added 526 mg of 60% sodium hydride, and the mixture was stirred for 25 minutes. Then, 3.21 g of triphenylmethyl chloride was added and the mixture was stirred at the same temperature for 15 minutes and further stirred at room temperature for 45 minutes. The reaction mixture was ice-cooled again, saturated aqueous sodium hydrogencarbonate solution was added and the mixture was extracted with 100 ml of ethyl acetate. The organic layer was sequentially washed with water (×2) and brine, dried over anhydrous magnesium sulfate and the solvent was evaporated. The crude product was purified and separated by silica gel column chromatography (ethyl acetate:hexane=1:9), and the resulting crystals were recrystallized from diisopropyl ether, to give 1.73 g of the title compound as white needles.

Workup

  1. stirringthe mixture was stirred at the same temperature for 15 minutes
  2. stirringfurther stirred at room temperature for 45 minutes
  3. temperaturecooled again
  4. extractionthe mixture was extracted with 100 ml of ethyl acetate
  5. washThe organic layer was sequentially washed with water (×2) and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated
  8. customThe crude product was purified
  9. customseparated by silica gel column chromatography (ethyl acetate:hexane=1:9)
  10. customthe resulting crystals were recrystallized from diisopropyl ether

Sources & evidence

ORD record
ord-dd0150347984417c968f747c4c5f4bb1
Source dataset
uspto-grants-2010_08
Patent number
US07776890B2

Reaction notes

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