The general procedure for the synthesis of 3,5-dimethylisoxazole-4-boronic acid from 4-bromo-3,5-dimethylisoxazole and triisopropyl borate is as follows:
Synthesis of intermediate 106 (3,5-dimethyl-1,2-oxazol-4-ylboronic acid):
1. A solution of 4-bromo-3,5-dimethyl-1,2-oxazole (4.0 g, 22.7 mmol) in THF (40 mL) was added to a 500 mL three-necked flask fitted with a magnetic stirrer and the reaction system was cooled to -78°C.
2. n-Butyllithium (28.4 mL, 1.6 M solution, 45.0 mmol) was added dropwise to the reaction system with stirring and stirring was continued for about 30 minutes at -65 °C.
3. the temperature of the reaction mixture was raised to -78 °C, followed by the addition of triisopropyl borate (12.81 g, 68.0 mmol).
4. After the temperature of the reaction system was brought to room temperature, stirring was continued for about 16 hours.
5. Upon completion of the reaction, the solvent was removed under reduced pressure, the reaction was quenched with saturated NH4Cl solution and extracted with ethyl acetate.
6. The organic layer was washed with water, dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure.
7. The crude product obtained was purified by silica gel column chromatography to finally obtain the target compound in white solid form (0.4 g, yield: 12.5%).
