Methanol → 4-(5-Methyl-1,3,4-oxadiazol-2-yl)benzoic acid

Participants

Reaction Steps

Oxalyl chloride (1.05 g, 8.3 mmol) was added to a stirred solution of terephthalic acid monomethyl ester (1 g, 5.55 mmol) in DCM (12 mL) and stirring was continued at ambient temperature for 4 hr. The reaction mixture was concentrated under reduced pressure to afford the residue. The residue was dissolved in DCM (4 mL) and to the resulting solution was added, acetic acid hydrazide (490 mg, 6.66 mmol), Et3N (670 mg, 6.66 mmol) and stirring was continued at temperature overnight. The reaction mixture was diluted with water and extracted with ethylacetate, dried over sodium sulfate and concentrated under reduced pressure to afford 1 g (76.39% Yield) of 4-(N′-acetyl-hydrazinocarbonyl)-benzoic acid methyl ester. A stirred solution of 4-(N′-acetyl-hydrazinocarbonyl)-benzoic acid methyl ester (500 mg, 5.55 mmol) in POCl3 (12 mL) was heated at 100° C. for 3 hr. The reaction mixture was concentrated under reduced pressure to afford the residue. The residue was diluted with cold water, extracted with ethyl acetate, washed the organic layer with sodium bicarbonate solution, saturated brine solution and dried over sodium sulfate. The organic layer was concentrated under reduced pressure to 350 mg (75.92% Yield) of afford 4-(5-methyl-[1,3,4]oxadiazol-2-yl)-benzoic acid methyl ester. LiOH.H2O (330 mg, 8 mmol) was added to a solution of 4-(5-methyl-[1,3,4]oxadiazol-2-yl)-benzoic acid methyl ester (350 mg, 1.6 mmol) in the mixture of methanol (4 mL), THF (10 mL) and H2O (4 mL). The resulting reaction mixture was stirred at ambient temperature for 2 hrs. The reaction mixture was concentrated The residue was diluted with water, acidified with aqueous citric acid solution, extracted with ethyl acetate and dried over sodium sulfate. The organic layer was concentrated under reduced pressure to afford 280 mg (87.46% Yield) of 4-(5-methyl-[1,3,4]oxadiazol-2-yl)-benzoic acid.

Provenance & Evidence