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

Benzoyl chloride (1.60 ml, 13.8 mmol) was added to a suspension of 2-chloro-N′-hydroxyacetimidamide (I44) (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 additional 30 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), and the combined organic phases were dried (Na2SO4), filtered and evaporated. The resulting residue is suspended in toluene (25 ml), and the mixture is heated to reflux for six hours and then at room temperature for two days. The dark solution was evaporated, and the crude product was purified by flash chromatography eluting with petroleum ether/EtOAc=95/5 to obtain 3-(chloromethyl)-5-phenyl-1,2,4-oxadiazole (803 mg, 44.8% yield) as a off-white solid.

1. stirringthe mixture was stirred for additional 30 minutes
2. additionwas added
3. extractionThe aqueous phase was extracted three times with DCM (15 ml)
4. dry with materialthe combined organic phases were dried (Na2SO4)
5. filtrationfiltered
6. customevaporated
7. temperaturethe mixture is heated
8. temperatureto reflux for six hours
9. waitat room temperature for two days
10. customThe dark solution was evaporated
11. customthe crude product was purified by flash chromatography
12. washeluting with petroleum ether/EtOAc=95/5

ORD record

ord-1c0687aacce948f0a064309f2b1f7749

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08563577B2