Preparation | 1) At room temperature, add NCS(2.7g,20 mmol) to the solution of acetaldoxime (1g,16.9 mmol) in anhydrous THF(15 mL). After stirring for 2 hours, slowly add the anhydrous THF(4 mL) dilution solution of propargyl alcohol (1.42g,25 mmol), and after 30 minutes, add the anhydrous THF dilution solution of TEA(2.78 mL,20 mmol). Add drop by drop. After 1 hour of vigorous stirring, water (10mL) was added to the reaction mixture. The suspension was extracted with EA(20mL × 3), the organic layer was dried by MgSO 4, filtered and vacuum concentrated. The residue was purified by silica gel rapid column chromatography (EA / Hex 1:1) to obtain (3-methylisoxazole-5-yl) methanol. Yield 0.93g,8.28mmol,49%. 2) Jones reagent (2.21mL) was added to acetone (19mL) solution of (3-methylisoxazol-5-yl) methanol (0.5g,4.42mmol) at 0 ℃, and the mixture was stirred for 3h. The reaction was monitored by TLC, and after the reaction was terminated, the pH of the mixture was adjusted to 2 with 1N HCl solution. The residue was extracted with EA(20mL × 3), and the combined organic layer was dried by MgSO4, filtered and vacuum concentrated. The residue was purified by silica gel rapid column chromatography (EA / Hex 1:1) to obtain the desired product 3-methylisoxazole-5-formic acid. Yield 0.63g,4.97mmol,100%. |