3-Fluorobenzoic Acid → 3-(chloromethyl)-5-(3-fluorophenyl)-1,2,4-oxadiazole

Participants

Reaction Conditions

Reaction Steps

DMF (10 ml) was added to a mixture of 3-fluorobenzoic acid (710 mg, 5.07 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (972 mg, 5.07 mmol), 1-hydroxybenzotriazole hydrate (HOBt) (685 mg, 5.07 mmol) and 2-chloro-N-hydroxy-acetamidine (500 mg, 4.61 mmol) at room temperature and then stirred overnight. The reaction mixture was diluted with ethyl acetate, washed with water (3 times) and brine, dried over anhydrous sodium sulfate, filtered and concentrated. DMF (14 ml) was added to the residue and the resulting solution was heated at 135° C. for 3.5 h to effect cyclization to oxadiazole. After cooling the reaction mixture was washed with water (3 times) and brine, dried over anhydrous sodium sulfate, filtered and concentrated. 3-Chloromethyl-5-(3-fluoro-phenyl)-[1,2,4]oxadiazole (383 mg, 35% yield over 2 steps, yellow oil) was obtained by flash chromatography on silica gel, using 5% ethyl acetate in hexane. 1H NMR (CDCl3), δ (ppm): 7.96 (d, 1H), 7.86 (m, 1H), 7.54 (m, 1H), 7.33 (m, 1H), 4.68 (s, 2H).

Provenance & Evidence