Chloride → 4-[3-(4-Methoxy-phenoxymethyl)-[1,2,4]oxadiazol-5-ylmethyl]-benzoic acid ethyl ester

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Reaction Steps

Add oxaxyl chloride (1.25 mL, 14 mmol) to 4-carboxymethyl-benzoic acid ethyl ester (365 mg, 1.75 mmol) in benzene (11 mL) and a drop of dimethylformamide at room temperature under argon gas over a 5 minute period. Stir the reaction mixture for 2 hours at room temperature. Concentrate the reaction mixture to an oil. Redissolve the oil in dimethylformamide (10 mL) and N-hydroxy-2-(4-methoxy-phenoxy)-acetamidine (380 mg, 1.9 mmol) is added. Stir the reaction mixture at room temperature for 3 hours. Heat the reaction mixture to 120° C. and stir for 7 hours. After cooling to room temperature, quench the reaction mixture with water and extract with ethyl acetate (3×). Combine the organic layers, wash with brine, dry over sodium sulfate, and concentrate. Purify the residue by flash column chromatography using 20% ethyl acetate/hexane to give the title compound (201 mg, 31%). LC-MS (m/e): 369 (M+1).

Provenance & Evidence