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

HRID 471375Notes

Reaction equation

HRID 471375 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.[C:29](Cl)(=O)[CH3:30].O.CCOC(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:29]([CH3:30])[O:21][N:20]=4)=[C:16]([CH3:24])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6367Acetyl chlorideHCID 8857Ethyl AcetateHCID 178423542HCID 178423542, compound2×

Product 1

HCID 674409963-{4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-phenyl}-5-methyl-[1,2,4]oxadiazoleYield 65.3%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

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, 400 mg, 0.93 mmol) in pyridine (10 mL) was added acetyl chloride (0.13 mL, 0.15 g, 1.85 mmol) via syringe and the mixture was stirred at reflux for 30 min. 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 (277 mg, 65%).

Workup

  1. temperatureat reflux for 30 min
  2. temperatureafter cooling
  3. extractionthe aqueous layer was extracted with EtOAc
  4. dry with materialCombined organic layers were dried (Na2SO4)
  5. concentrationconcentrated in vacuum
  6. customThe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-195bd69e1ff2463aa772bc74d3412952
Source dataset
uspto-grants-2014_01
Patent number
US08633134B2

Reaction notes

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