An efficient synthesis of a dual PPAR alpha/gamma agonist and the formation of a sterically congested alpha-aryloxyisobutyric acid via a Bargellini reaction

A practical synthesis of benzisoxazole and its conversion to alpha-aryloxyisobutyric acid using 1,1,1-trichloro-2-methyl-2-propanol is developed. A highly reactive, short-lived intermediate derived from chloretone is detected by ReacIR and its half-life determined to be ~5 min.