1,4-Dioxane dibromide → 2-(5-bromoacetyl-2-ethoxyphenyl)-8-methylquinazolin-4(3H)-one

Participants

Reaction Steps

A solution of 1,4-dioxane dibromide (0.5 g, 0.002 mol) in 1,4-dioxane (10 ml) was added dropwise to a stirred solution of 2-(5-acetyl-2-ethoxyphenyl)-8-methylquinazolin-4(3H)-one (Preparation 15; 0.64 g, 0.002 mol) in 1,4-dioxane (40 ml) and the resulting mixture heated under reflux for 2 hours. The precipitate which formed in the cool reaction mixture was collected by filtration, washed with 1,4-dioxane followed by diethyl ether, and air-dried to give 2-(5-bromoacetyl-2-ethoxyphenyl)-8-methylquinazolin-4(3H)-one, which was used without further purification. The crude bromoacetyl intermediate was suspended in stirred acetonitrile (40 ml) and morpholine (0.174 g, 0.002 mol) added; after 1.5 hours at room temperature, the solvent was evaporated under vacuum. The residue was suspended in water (20 ml) and the suspension extracted with dichloromethane (3×20 ml), then the extracts were combined, dried (Na2SO4) and evaporated under vacuum. The residue was chromatographed on silica gel using a methanol in dichloromethane elution gradient (0-1%) and then the product crystallized from ethyl acetate-hexane to give the title compound as a white powder (0.29 g, 36%), m.p. 172-173° C.

Provenance & Evidence