Ethyl Acetate → 2-(3-(3-Fluorophenyl)-1H-5-indazolyl]acetonitrile

HRID 1610077Notes

Reaction equation

HRID 1610077 reaction equation
Cl[CH2:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8](C(OC(C)(C)C)=O)[N:7]=[C:6]2[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=1.[C-:26]#[N:27].[Na+].C(OCC)(=O)C>CS(C)=O>[F:25][C:21]1[CH:20]=[C:19]([C:6]2[C:5]3[C:9](=[CH:10][CH:11]=[C:3]([CH2:2][C:26]#[N:27])[CH:4]=3)[NH:8][N:7]=2)[CH:24]=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 8929Sodium CyanideHCID 222606161h-Indazole-1-carboxylic acid,5-(chloromethyl)-3-(3-fluorophenyl)-,1,1-dimethylethyl ester

Product 1

HCID 222606222-(3-(3-Fluorophenyl)-1H-5-indazolyl]acetonitrileYield 8.9%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 1.0 g of tert-butyl 5-(chloromethyl)-3-(3-fluorophenyl)-1H-1-indazolecarboxylate in 5 ml dimethyl sulfoxide was added 204 mg of sodium cyanide, and the mixture was stirred at room temperature for 50 minutes. To the reaction mixture was added 50 ml of ethyl acetate, and after washing with water, the aqueous layer was re-extracted with diethyl ether. The collected 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:toluene=1:9), and suspended in diethyl ether-diisopropyl ether, to give 62 mg of the title compound as yellow crystals.

Workup

  1. washafter washing with water
  2. extractionthe aqueous layer was re-extracted with diethyl ether
  3. washThe collected organic layer was sequentially washed with water (×2) and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated
  6. customThe crude product was purified
  7. customseparated by silica gel column chromatography (ethyl acetate:toluene=1:9)

Sources & evidence

ORD record
ord-85180c3edad642a5bf2f30da6aedbd7a
Source dataset
uspto-grants-2006_01
Patent number
US06982274B2

Reaction notes

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