Tetramethylene sulfoxide → 4-[5-(3,5-Dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-methyl-N-methyl-N-(2-tetrahydrothienyl)benzoic acid amide

HRID 910398

Reaction equation

HRID 910398 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:25]([F:28])([F:27])[F:26])[O:13][N:12]=[C:11]([C:14]3[CH:23]=[CH:22][C:17]([C:18]([NH:20][CH3:21])=[O:19])=[C:16]([CH3:24])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.C(N(CC)CC)C.[S:36]1(=O)[CH2:40][CH2:39][CH2:38][CH2:37]1>C1(C)C=CC=CC=1.[I-].[Zn+2].[I-]>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:25]([F:27])([F:26])[F:28])[O:13][N:12]=[C:11]([C:14]3[CH:23]=[CH:22][C:17]([C:18]([N:20]([CH3:21])[CH:37]4[CH2:38][CH2:39][CH2:40][S:36]4)=[O:19])=[C:16]([CH3:24])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

6

Reactant 3

HCID 1128Tetramethylene sulfoxideHCID 8471TriethylamineHCID 667843434-(5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N,2-dimethylbenzamide

Product 1

HCID 667843884-[5-(3,5-Dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-methyl-N-methyl-N-(2-tetrahydrothienyl)benzoic acid amideYield 18.1%

Reagents, catalysts & solvents 2

HCID 9883512zinc(II)iodideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

In a solution of 0.43 g of 4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole-3-yl]-2-methyl-N-methyl benzoic acid amide synthesized similarly to Synthetic Example 29 and 0.20 g of triethylamine in 5 ml of toluene, 0.45 g of trimethyl silyl trifurate was added and stirred vigorously. 10 minutes after the stirring, the reaction mixture was cooled to 0° C., 0.10 g of tetrahydrothiophene-1-oxide and 0.06 g of zinc iodide were added with stirring, and continued to stir at room temperature further for 4 days. After the completion of the reaction, 10 ml of ice water was added in the reaction mixture, and extracted with ethyl acetate (20 ml×2), the organic phase was dehydrated and dried with saturated sodium chloride aqueous solution and anhydrous sodium sulfate in that order, and the solvent was distilled under reduced pressure. The residue was purified with silica gel column chromatography that was eluated with ethyl acetate-hexane (1:2) to obtain 0.09 g of the aimed product as white crystal.

Workup

  1. additionwas added
  2. stirringwith stirring
  3. stirringto stir at room temperature further for 4 days
  4. additionwas added in the reaction mixture
  5. extractionextracted with ethyl acetate (20 ml×2)
  6. dry with materialdried with saturated sodium chloride aqueous solution and anhydrous sodium sulfate in that order
  7. distillationthe solvent was distilled under reduced pressure
  8. customThe residue was purified with silica gel column chromatography that

Sources & evidence

ORD record
ord-d733ab67efbe431eba4e2a8f5bde9f9d
Source dataset
uspto-grants-2011_09
Patent number
US08022089B2

Linked notes

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