Acetyl chloride → N-acetyl-N-(5-chloro-2-pyrimidinyl)-4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole-3-yl]-2-methyl benzoic acid amide

HRID 878814Notes

Reaction equation

HRID 878814 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([NH:8][C:9](=[O:34])[C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH2:20][C:19]([C:25]4[CH:30]=[C:29]([Cl:31])[CH:28]=[C:27]([Cl:32])[CH:26]=4)([C:21]([F:24])([F:23])[F:22])[O:18][N:17]=3)=[CH:12][C:11]=2[CH3:33])=[N:6][CH:7]=1.[H-].[Na+].[H][H].[C:39](Cl)(=[O:41])[CH3:40]>O1CCCC1>[C:39]([N:8]([C:5]1[N:4]=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=1)[C:9](=[O:34])[C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH2:20][C:19]([C:25]3[CH:26]=[C:27]([Cl:32])[CH:28]=[C:29]([Cl:31])[CH:30]=3)([C:21]([F:23])([F:24])[F:22])[O:18][N:17]=2)=[CH:12][C:11]=1[CH3:33])(=[O:41])[CH3:40]

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 24758Sodium hydrideHCID 86654456N-(5-chloro-2-pyrimidinyl)-4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl benzoic acid amideHCID 178418361HCID 178418361, compound

Product 1

HCID 25217022N-acetyl-N-(5-chloro-2-pyrimidinyl)-4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole-3-yl]-2-methyl benzoic acid amideYield 46.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a solution of 0.20 g of N-(5-chloro-2-pyrimidinyl)-4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-methyl benzoic acid amide in 3 mL of tetrahydrofuran, 0.025 g of 55% oily sodium hydride was added under cooling with ice and with stirring and stirred at room temperature for 10 minutes. After ceasing the generation of hydrogen gas, 0.045 g of acetyl chloride was added under cooling with ice and with stirring, and continued to stir at the same temperature further for 1 hour. After the completion of the reaction, the reaction mixture was poured in 10 mL of ice water, extracted with ethyl acetate (10 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 (gradient of 1:9 to 3:7) to obtain 0.10 g of the aimed product as white crystal.

Workup

  1. temperatureunder cooling with ice
  2. stirringstirred at room temperature for 10 minutes
  3. additionwas added
  4. temperatureunder cooling with ice
  5. stirringwith stirring
  6. stirringto stir at the same temperature further for 1 hour
  7. customAfter the completion of the reaction
  8. extractionextracted with ethyl acetate (10 mL×1)
  9. dry with materialdried over saturated sodium chloride aqueous solution
  10. distillationanhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure
  11. customThe residue was purified with silica gel column chromatography that

Sources & evidence

ORD record
ord-79a4616001624cb3887574423fa46f75
Source dataset
uspto-grants-2015_03
Patent number
US08987464B2

Reaction notes

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