Benzoyl chloride → 3-(Chloromethyl)-5-phenyl-1,2,4-oxadiazole

HRID 404619Notes

Reaction equation

HRID 404619 reaction equation
[C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:10][CH2:11][C:12](=[N:14]O)[NH2:13]>C(Cl)Cl.O>[Cl:10][CH2:11][C:12]1[N:14]=[C:1]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[O:8][N:13]=1

Participants

5

Reactant 2

HCID 7412Benzoyl chlorideHCID 41122522-chloro-N'-hydroxyethanimidamide

Product 1

HCID 3021543-(Chloromethyl)-5-phenyl-1,2,4-oxadiazoleYield 44.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

Benzoyl chloride (1.60 ml, 13.8 mmol) was added to a suspension of 2-chloro-N′-hydroxyacetimidamide (1.0 g, 9.21 mmol) in DCM (25 ml), with stirring at room temperature. After 30 minutes, TEA (1.41 ml, 10.1 mmol) was added to the white suspension and the mixture was stirred for 30 additional minutes (UPLC-MS: complete conversion). The solution was diluted with DCM (20 ml) and water (30 ml) was added. The aqueous phase was extracted three times with DCM (15 ml×3) and then the combined organic phases were dried (Na2SO4) and evaporated. The crude was suspended in toluene (25 ml) and the mixture was heated to reflux for 6 h (UPLC-MS: complete conversion). The solvent was evaporated and the crude was purified by flash chromatography (petroleum ether/EtOAc=95/5) to obtain 3-(chloromethyl)-5-phenyl-1,2,4-oxadiazole (803 mg, 44.8% yield) as an off-white solid.

Workup

  1. stirringthe mixture was stirred for 30 additional minutes (UPLC-MS: complete conversion)
  2. additionwas added
  3. extractionThe aqueous phase was extracted three times with DCM (15 ml×3)
  4. dry with materialthe combined organic phases were dried (Na2SO4)
  5. customevaporated
  6. temperaturethe mixture was heated
  7. temperatureto reflux for 6 h (UPLC-MS: complete conversion)
  8. customThe solvent was evaporated
  9. customthe crude was purified by flash chromatography (petroleum ether/EtOAc=95/5)

Sources & evidence

ORD record
ord-031cd1f1b49c48b4b287179e59899b42
Source dataset
uspto-grants-2014_06
Patent number
US08748613B2

Reaction notes

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