Application
3-Methylisoxazole-5-carboxylic acid is an organic intermediate that can be prepared by first cyclizing acetaldehyde oxime and propargyl alcohol to prepare (3-methylisoxazole-5-yl)methanol, and then oxidizing it to obtain 3-methylisoxazole-5-carboxylic acid.
Synthesis
General procedure for the synthesis of 3-methylisoxazole-5-carboxylic acid from methyl 3-methyl-5-isoxazolecarboxylate: To a round bottom flask equipped with a magnetic stirrer was added a solution of methyl 3-methyl-5-isoxazolecarboxylate (900 mg, 5.8 mmol) in tetrahydrofuran (2.0 mL). Subsequently, a solution of sodium hydroxide (465 mg, 11.6 mmol) in water (2 mL) was added dropwise to the reaction system and methanol (4 mL) was added. The reaction mixture was stirred at room temperature for 18-20 hours under argon protection. Upon completion of the reaction, the mixture was transferred to a partition funnel and the pH was adjusted to 2 with 1 N hydrochloric acid solution. the aqueous phase was extracted with ethyl acetate (3 x 35 mL), the organic phases were combined and washed with saturated brine (50 mL), dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to afford 3-methylisoxazole-5-carboxylic acid as a white solid (660 mg, 90% yield). The obtained product did not need further purification and could be used directly in the next reaction.
References
[1] Angewandte Chemie - International Edition, 2016, vol. 55, # 29, p. 8353 - 8357
[2] Angew. Chem., 2016, vol. 128, # 29, p. 8493 - 8497,5
[3] Patent: WO2006/91674, 2006, A1. Location in patent: Page/Page column 79
[4] European Journal of Medicinal Chemistry, 1992, vol. 27, # 6, p. 581 - 593
