Background and overview[1]
(Trimethylisoxazol-5-yl)methanol is an alcohol derivative that can be used as a pharmaceutical synthesis intermediate.
Structure
Preparation[1]
1) Add NCS (2.7g, 20mmol) to a solution of acetaldoxime (1g, 16.9mmol) in anhydrous THF (15mL) at room temperature. After stirring for 2 hours, a dilute solution of propargyl alcohol (1.42 g, 25 mmol) in anhydrous THF (4 mL) was slowly added, and after 30 minutes, a dilute solution of TEA (2.78 mL, 20 mmol) in anhydrous THF was added. Then add continuously. After 1 hour with vigorous stirring, water (10 mL) was added to the reaction mixture. The suspension was extracted with EA (20 mL × 3), the organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel flash column chromatography (EA/Hex 1:1) to give (3-methylisoxazol-5-yl)methanol.
(0.93g, 8.28mmol, 49%). 1HNMR (300MHz, CDCl3) δ6.09 (s, 1H), 4.73 (s, 2H), 2.52 (br, 1H), 2.34 (s, 3H). 13CNMR (75MHz, CDCl3) δ171.09, 159.85, 102.53, 56.46, 11.37.
Apply[1]
(Trimethylisoxazol-5-yl)methanol, for example, prepare the following compound:
(Trimethylisoxazol-5-yl)methanol (0.5g, 4.42) was added to acetone (19mL) at 0°C and Jones reagent (2.21mL) was added, and the mixture was stirred for 3 hours. The reaction was monitored by TLC and after the reaction was terminated, the mixture was adjusted to pH 2 with 1 N HCl solution. The residue was extracted with EA (20 mL×3), and the combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel flash column chromatography (EA/Hex 1:1) to give the desired product (0.63 g, 4.97 mmol, 100%). 1HNMR (300MHz, CH3OD) δ6.90 (s, 1H), 2.35 (s, 3H). 13CNMR (75MHz, CH3OD) δ161.05, 160.82, 158.16, 109.46, 98.81.
