Nitrogen → 1-(2,4-Dichlorobenzyl)-6-trifluoromethyl-1H-indazole-3-carboxylic Acid methyl ester

HRID 388625Notes

Reaction equation

HRID 388625 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:11][CH:12]=2)[NH:7][N:6]=1)=[O:4].C(=O)([O-])[O-].[K+].[K+].[Cl:24][C:25]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:26]=1[CH2:27]Cl.N#N>C(#N)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([C:14]([F:17])([F:15])[F:16])=[CH:11][CH:12]=2)[N:7]([CH2:27][C:26]2[CH:29]=[CH:30][C:31]([Cl:33])=[CH:32][C:25]=2[Cl:24])[N:6]=1)=[O:4]

Participants

7

Reactant 4

HCID 947NitrogenHCID 72122,4-Dichlorobenzyl chlorideHCID 11430Potassium Carbonate2×HCID 53408454Methyl 6-(trifluoromethyl)-1H-indazole-3-carboxylate

Product 1

HCID 115242041-(2,4-Dichlorobenzyl)-6-trifluoromethyl-1H-indazole-3-carboxylic Acid methyl ester

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6342AcetonitrileSolvent

Procedure

6-Trifluoromethyl-1H-indazole-3-carboxylic acid methyl ester (2.75 g, 0.0112 mol) was dissolved in acetonitrile (50 mL), and potassium carbonate (10 g, 0.07 mol), 2,4-dichlorobenzyl chloride (2.42 g, 0.01239 mol) and tetrabutylammonium iodide (catalytic) were added. The reaction mixture was heated to reflux and refluxed for 2 h under good stirring. The progress of the reaction was monitored by TLC. After completion of the reaction, potassium carbonate was filtered while hot and then washed with acetone. The combined solvents were distilled off under reduced pressure to afford the crude mixture of N1 and N2 benzylated products. The isomers were separated by column chromatography (silica gel, eluent started with hexane then changed to 8:2 hexane, ethyl acetate).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux
  3. temperaturerefluxed for 2 h under good stirring
  4. filtrationwas filtered while hot and
  5. washthen washed with acetone
  6. distillationThe combined solvents were distilled off under reduced pressure
  7. customto afford the crude
  8. customThe isomers were separated by column chromatography (silica gel, eluent

Sources & evidence

ORD record
ord-7b72b867b9c04661a9bae994f8f73465
Source dataset
uspto-grants-2013_02
Patent number
US08377958B2

Reaction notes

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