Phosphorus oxychloride → 2-(Chloromethyl)-5-(4-chlorophenyl)-1,3,4-oxadiazole

To a mixture of 4-chlorobenzohydrazide 5 (1 g, 5.86 mmol) and K2CO3 (0.97 g, 7.03 mmol) in acetonitrile (30 mL) was added 2-chloroacetyl chloride (0.68 g, 6.08 mmol) dropwise at ambient temperature. The resulting mixture was stirred at ambient temperature for 16 hours. The solid was collected, washed with H2O and ether, and dried to afford 4-chloro-N′-(2-chloroacetyl)benzohydrazide 6 (1.2 g, 82%) which was used for the next step without further purification. A mixture of 4-chloro-N′-(2-chloroacetyl)benzohydrazide 6 (0.6 g, 2.43 mmol) and phosphorous oxychloride (0.37 g, 2.43 mmol) in acetonitrile (20 mL) was stirred under reflux for 16 hours and concentrated. The residue was subjected to flush column chromatography eluting with 10-25% acetone/hexanes to give compound 7 (0.45 g). Yield: 82%.

1. customwas used for the next step without further purification
2. temperatureunder reflux for 16 hours
3. concentrationconcentrated
4. customto flush column chromatography
5. washeluting with 10-25% acetone/hexanes

ORD record

ord-403a30879bc547fca00d9fe10fd8f003

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08883827B2