Uses
5-Isoxazolecarboxylic Acid Methyl Ester is used as a reagent in the synthesis of pyridine derivatives as integrase inhibitors and antiviral agents. 5-Isoxazolecarboxylic Acid Methyl Ester is also a useful synthetic intermediate in the preparation of pyrazolopyrimidine derivatives useful in the prevention and treatment of cancer.
Synthesis
A mixture of isoxazole-5-carboxylic acid (2.5 g, 22.1 mmol), sodium bicarbonate (5.57 g, 66.32 mmol) and iodomethane (8.26 mL, 132.65 mmol) in N,N-dimethylformamide (DMF, 30 mL) was stirred and reacted for 19 hr at 25 °C. After completion of the reaction, the mixture was diluted with deionized water (30 mL) and extracted with ether (2 × 50 mL). The combined organic layers were washed with saturated saline, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the crude product. The crude product was purified by a Biotage fast chromatography system (40 m column) with the eluent of ethyl acetate-hexane (1:2, v/v), followed by switching to pure ethyl acetate, resulting in methyl isoxazole-5-carboxylate as an amorphous solid (1.2 g, 42.7% yield). Mass spectrum (+ESI): m/z 128 [M+H]+.
