Preparation background and overview of 3,5-dimethylisoxazole-4-boronic acid
The Chinese alias of 3,5-dimethylisoxazole-4-boronic acid is 3,5-dimethylisoxazole-4-boronic acid, CAS number 6114-47-9, chemical formula C5H8BNO3. Molecular weight 140.93300. White to light yellow crystal powder, density 1.23 g/cm3, boiling point 334ºC at 760 mmHg, melting point 108-113 °C, flash point 155.8ºC, refractive index 1.486, vapor pressure 0mmHg at 25°C. 3,5-Dimethylisoxazole-4-boronic acid can be used as a pharmaceutical and chemical synthesis intermediate.
Preparation structure of 3,5-dimethylisoxazole-4-boronic acid
Preparation of 3,5-dimethylisoxazole-4-boronic acid
Step 1: Synthesis of 4-bromo-3,5-dimethyl-1,2-oxazole
Add DMF (53 mL) to a 250 mL RB flask equipped with a magnetic stirrer. Add 3,5-dimethyl-1,2-oxazole (5.3g, 54.57mmol) and N-iodosuccinimide (11.659g, 65.49m aminopyridine ol) to the stirring solvent. After addition, The reaction mixture was heated at 75°C for 3 minutes. H. After the reaction was completed, the reaction mixture was diluted with ethyl acetate (100 mL), and the organic layer was washed with saturated NaHCO solution (100 mL), thiosulfate solution (100 mL), water (200 mL), and finally with brine solution. (100ml). The organic layer was dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure to obtain the product (6.1 g, yield: 63.4%).
Step 2: Synthesis of 3,5-dimethylisoxazole-4-boronic acid
Add a solution of 4-bromo-3,5-dimethyl-1,2-oxazole (4.0g, 22.7mmol) in THF (40mL) to a 500mL triple RB flask equipped with a magnetic stirrer, and cool to -78℃. Add n-butyllithium (28.4 mL, 1.6 M solution, 45.0 mmol) dropwise to the stirring solvent and stir at -65 °C for approximately 30 min. Raise the RM to -78 °C, add triisopropylborate (12.81 g, 68.0 mmol) once the temperature reaches room temperature and stir for approximately 16 h. The solvent was then removed under reduced pressure and quenched with saturated NH4Cl solution and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude material obtained was purified by silica gel column chromatography to obtain 3,5-dimethylisoxazole-4-boronic acid as a white solid. (0.4g, yield: 12.5%).
Main reference materials
[1] CONNEXIOS LIFE SCIENCES PVT. LTD.; RANGANATH RAO PROPYL CARBONATE, Jagannath Madanahalli; ARUMUGAM, Nagarajan; ANSARI, Mohd Mudabbir; GUDLA, Chandrasekhar; PACHIYAPPAN, Shanmugam; RAMALINGAM, Manivannan; GEORGE, Jenson; ARUL , George Fernanda; BOMMEGOWDA, Y, Kenchegowda; ANGUPILLAI, Sathesh Kumar; KOTTAMALAI, Ramamoorthy; JIDUGU, Pradeep; RAO, D, Shivanageshwara Patent: WO2012/11125 A1, 2012; Location in patent: Page/Page column 148-149; 2012/011125 A1
