Preparation background and overview of phenyl-D5-boronic acid
Phenyl-D5-boronic acid is a boronic acid compound that can be used in the Suzuki reaction. There are reports in the literature that phenyl-D5-boronic acid can be obtained from deuterated bromobenzene or deuterated fluorobenzene in one step.
Preparation of phenyl-D5-boronic acid
Preparation report of phenyl-D5-boronic acid 1.
Dissolve 0.05 mol of the intermediate deuterated bromobenzene in 40 ml of THF solvent, cool to -78°C, add lithium reagent dropwise, maintain the temperature for 1 hour after completion, and add borate ester dropwise. Then naturally raise the temperature to 25°C. After 1 hour, HPLC detected that the reaction of the raw materials was basically completed. The reaction solution was evaporated under reduced pressure, and the residue was subjected to column chromatography to obtain phenyl-D5-boronic acid (yield: 64%).
Preparation report of phenyl-D5-boronic acid 2.
Add pentadeuterated fluorobenzene (0.50g) and tetrahydrofuran (10.00ml) into a 50ml two-neck flask, replace the system with nitrogen, cool to -70°C and stir, and add tert-butyllithium solution (4.05ml) for 7 minutes. ) was added dropwise to the reaction system. After the dripping was completed, stir for 1 hour. Add trimethyl borate (0.57g) dropwise to the reaction system over 1-2 minutes. Keep stirring for 4 hours. Take a sample and send it to HPLC until the reaction is complete. Raise the temperature to room temperature and let it stand for 16 hours. , take samples and send to HPLC. Adjust the pH of the reaction solution to 1-2 with 10% hydrochloric acid at room temperature, stir for 0.5h and then extract three times with 15ml of methyl tert-butyl ether. Combine the organic phases, dry over anhydrous sodium sulfate, filter, and spin the filtrate to obtain 0.4g. Off-white solid, yield 56.20%.
Preparation report 3 of phenyl-D5-boronic acid,
Step 1, synthesis of d5-bromobenzene (compound 36).
Add concentrated sulfuric acid (11.89g, 6.5mL) to the reaction flask, add 24mL of water to dilute, cool to 0°C, add deuterated benzene (3g, 0.035mol) dropwise, after the dropwise addition, add twice at 0°C Add sodium bromate (5.92g, 0.039mol), react at room temperature for 18 hours, add 50mL of ice water, extract three times with n-hexane, combine the organic phases, wash with saturated sodium bicarbonate, saturated sodium chloride, and anhydrous sulfur tricyclic Hexylphosphine fluoroborate sodium hydrochloride was dried and concentrated below 30°C to obtain 2.38 g of compound 36, with a yield of 41.8%.
Step 2, d5-phenylboronic acid (compound 37) is synthesized into boronic acid.
Add compound 36 (2.379g, 14.68mmol), pinacol diborate (5.5g, 21mmol), and Pd(dppf)Cl2 (1.04g, 4.4mmol) and potassium acetate (4.2g, 43.5mmol), add 100mL of anhydrous dioxane under nitrogen protection, heat to 88°C and stir for 6 hours. TLC detects that the raw material reaction is complete, add 100mL of ethyl acetate to dilute, and concentrate to obtain Oily liquid, purified by column chromatography to obtain 1.5 g of compound 37, with a yield of 81.5%.
References
[1] [Chinese invention] CN201710868267.6 Triazine compounds containing deuterated phenyl groups and their applications and organic electroluminescent devices
[2] [Invented in China] CN201710311939.3 A synthesis method of deuterated nolazan fumarate metabolite
[3] WO2017152755 – Substituted biphenyl compound and pharmaceutical composition thereof
