Water → 3-{4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-trifluoroethyl-phenyl}-5-methyl-[1,2,4]oxadiazole

HRID 471376Notes

Reaction equation

HRID 471376 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][OH:21])=[NH:19])=[C:16]([CH3:24])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[F:29][C:30]([F:36])([F:35])CC(Cl)=O.O.[CH3:38][CH2:39]OC(C)=O>N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:25]([F:26])([F:28])[F:27])[O:13][N:12]=[C:11]([C:14]3[CH:23]=[CH:22][C:17]([C:18]4[N:19]=[C:38]([CH3:39])[O:21][N:20]=4)=[C:16]([CH2:24][C:30]([F:36])([F:35])[F:29])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 27833433,3,3-Trifluoropropionyl chlorideHCID 178423542HCID 178423542, compound

Product 1

HCID 866585243-{4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-trifluoroethyl-phenyl}-5-methyl-[1,2,4]oxadiazoleYield 53%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-N-hydroxy-2-methyl-benzamidine (i.e product of Step 1, Example 8, 400 mg, 0.93 mmol) in pyridine (10 mL) was added 3,3,3-trifluoropropionic acid chloride (0.271 g, 1.85 mmol) via syringe and the mixture was stirred at reflux for 30 min and at 140° C. in a microwave oven for 1 h. Water and EtOAc were added after cooling and the aqueous layer was extracted with EtOAc. Combined organic layers were dried (Na2SO4) and concentrated in vacuum. The residue was purified by flash chromatography on silica gel and yielded the title compound (260 mg, 53%).

Workup

  1. temperatureafter cooling
  2. extractionthe aqueous layer was extracted with EtOAc
  3. dry with materialCombined organic layers were dried (Na2SO4)
  4. concentrationconcentrated in vacuum
  5. customThe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-9e65182763f4472a9f5ed2838566f012
Source dataset
uspto-grants-2014_01
Patent number
US08633134B2

Reaction notes

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