Ethanol → 5-Chloromethyl-3-[2-(5-methyl-2-phenyl-4-oxazolyl)ethyl]-1,2,4-oxadiazole

Participants

Reaction Steps

A mixture of 3-(5-methyl-2-phenyl-4-oxazolyl)propionitrile (8.20 g), hydroxylammonium chloride (4.02 g), potassium carbonate (4.01 g) and 70% ethanol (100 mL) was heated under reflux for 24 hrs. The reaction mixture was concentrated and water was added to the residue. The obtained crystals were collected by filtration and washed with isopropyl ether. To a mixture of the obtained crystal, potassium carbonate (2.13 g) and acetone (50 mL) was added chloroacetyl chloride (3.48 g) under ice-cooling. The reaction mixture was stirred at room temperature for 15 hrs. Water was added to the reaction mixture, and the precipitated crystals were collected by filtration and washed with isopropyl ether. A mixture of the obtained crystals and xylene (150 mL) was subjected to azeotropic dehydration for 4 hrs. The reaction mixture was concentrated, and ethyl acetate was added to the residue. The organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The obtained residue was subjected to silica gel column chromatography to give crystals (2.56 g, 23%) of 5-chloromethyl-3-[2-(5-methyl-2-phenyl-4-oxazolyl)ethyl]-1,2,4-oxadiazole from a fraction eluted with ethyl acetate-hexane (1:4, v/v). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 71-72° C.

Provenance & Evidence