4-[5-(3,5-Dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole-3-yl]-2-fluoro benzoic acid → N-benzyl-4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-fluoro benzoic acid amide

HRID 910350Notes

Reaction equation

HRID 910350 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:24]([F:27])([F:26])[F:25])[O:13][N:12]=[C:11]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[C:16]([F:23])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1>ClCCl.C(Cl)(=O)C(Cl)=O.CN(C)C=O>[CH2:11]([NH:12][C:18](=[O:20])[C:17]1[CH:21]=[CH:22][C:14]([C:11]2[CH2:10][C:9]([C:4]3[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=3)([C:24]([F:27])([F:26])[F:25])[O:13][N:12]=2)=[CH:15][C:16]=1[F:23])[C:14]1[CH:22]=[CH:21][CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 1

HCID 866114634-[5-(3,5-Dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole-3-yl]-2-fluoro benzoic acid

Product 1

HCID 23634396N-benzyl-4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-fluoro benzoic acid amideYield 154.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 65578Oxalyl chlorideSolvent

Procedure

In a solution of 0.15 g of 4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole-3-yl]-2-fluoro benzoic acid in 10 ml of dichloromethane, 0.3 ml of oxalyl chloride and 2 drops of N,N-dimethylformamide were added at room temperature, and stirred at the same temperature for 10 minutes. After the completion of the reaction, the solvent was distilled off under reduced pressure, the remaining white solid was dissolved in 10 ml of chloroform, and 0.3 ml of benzylamine and then 0.3 ml of triethylamine were added under cooling with ice, after the completion of the addition, continued to stir at room temperature for further 20 minutes. After the completion of the reaction, 40 ml of water was poured in the reaction mixture, and extracted with ethyl acetate (50 ml×1). The organic phase was dehydrated with saturated sodium chloride aqueous solution and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified with silica gel column chromatography that was eluated with ethyl acetate-hexane (1:2) to obtain 0.14 g of the aimed product as white crystal.

Workup

  1. customAfter the completion of the reaction
  2. distillationthe solvent was distilled off under reduced pressure
  3. dissolutionthe remaining white solid was dissolved in 10 ml of chloroform
  4. addition0.3 ml of benzylamine and then 0.3 ml of triethylamine were added
  5. temperatureunder cooling with ice
  6. additionafter the completion of the addition
  7. stirringto stir at room temperature for further 20 minutes
  8. customAfter the completion of the reaction, 40 ml of water
  9. additionwas poured in the reaction mixture
  10. extractionextracted with ethyl acetate (50 ml×1)
  11. dry with materialdried over anhydrous sodium sulfate
  12. distillationthe solvent was distilled off under reduced pressure
  13. customThe residue was purified with silica gel column chromatography that

Sources & evidence

ORD record
ord-b2f99124d6964a8ba1d5e3f3766ada96
Source dataset
uspto-grants-2011_09
Patent number
US08022089B2

Reaction notes

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