Water → 4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazole-3-yl]-2-methyl-N-(2,2,2-trifluoroethoxymethyl)benzoic acid amide

HRID 552640Notes

Reaction equation

HRID 552640 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:26]([F:29])([F:28])[F:27])[O:13][N:12]=[C:11]([C:14]3[CH:24]=[CH:23][C:17]([C:18]([NH:20][CH2:21][OH:22])=[O:19])=[C:16]([CH3:25])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.S(Cl)(Cl)=O.O>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:26]([F:27])([F:29])[F:28])[O:13][N:12]=[C:11]([C:14]3[CH:24]=[CH:23][C:17]([C:18]([NH:20][CH2:21][O:22][CH2:9][C:26]([F:29])([F:28])[F:27])=[O:19])=[C:16]([CH3:25])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

5

Reactant 3

HCID 962WaterHCID 24386Thionyl ChlorideHCID 667853564-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-methyl-N-(hydroxymethyl) benzoic acid amide

Product 1

HCID 252170234-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazole-3-yl]-2-methyl-N-(2,2,2-trifluoroethoxymethyl)benzoic acid amideYield 119.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a solution of 1.70 g of 4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole-3-yl]-2-methyl-N-(hydroxymethyl)benzoic acid amide in 20 mL of dichloromethane, 0.68 g of thionyl chloride was added at room temperature with stirring, and stirred at the same temperature for 2 hours. Then, the solvent was distilled off under reduced pressure, and the residue was dissolved in 10 mL of tetrahydrofuran. 1.50 g of 2,2,2-trifluoroethanol was added dropwise in a suspension of 0.33 g of 60% oily sodium hydride in 30 mL of tetrahydrofuran under cooling with ice and with stirring, and stirred at the same temperature for 10 minutes. Then, in this reaction mixture, the tetrahydrofuran solution of benzoic acid chloride prepared above was added dropwise under cooling with ice and with stirring. After the completion of the addition dropwise, it was continued to stir at room temperature for 1 hour. After the completion of the reaction, 50 mL of water was added in the reaction mixture, extracted with ethyl acetate (70 mL×1), the organic phase was dehydrated with and dried over saturated sodium chloride aqueous solution and then anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified with silica gel column chromatography that was eluated with ethyl acetate-hexane (2:3) to obtain 1.20 g of the aimed product as colorless resinous substance.

Workup

  1. stirringstirred at the same temperature for 2 hours
  2. distillationThen, the solvent was distilled off under reduced pressure
  3. dissolutionthe residue was dissolved in 10 mL of tetrahydrofuran
  4. addition1.50 g of 2,2,2-trifluoroethanol was added dropwise in a suspension of 0.33 g of 60% oily sodium hydride in 30 mL of tetrahydrofuran
  5. temperatureunder cooling with ice
  6. stirringwith stirring
  7. stirringstirred at the same temperature for 10 minutes
  8. customThen, in this reaction mixture, the tetrahydrofuran solution of benzoic acid chloride prepared
  9. additionabove was added dropwise
  10. temperatureunder cooling with ice
  11. stirringwith stirring
  12. additionAfter the completion of the addition dropwise
  13. stirringto stir at room temperature for 1 hour
  14. additionwas added in the reaction mixture
  15. extractionextracted with ethyl acetate (70 mL×1)
  16. dry with materialdried over saturated sodium chloride aqueous solution
  17. distillationanhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure
  18. customThe residue was purified with silica gel column chromatography that

Sources & evidence

ORD record
ord-d67312b366da4d42a785ea13d9ad8bba
Source dataset
uspto-grants-2011_05
Patent number
US07951828B1

Reaction notes

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