Preparation background and overview of B-[2-(9H-carbazol-9-yl)phenyl]boronic acid
B-[2-(9H-carbazol-9-yl)phenyl]boronic acid can be used as a pharmaceutical synthesis intermediate, and can be used to prepare 9-(2- Bromophenyl)-9H-carbazole is prepared by further reacting with n-butyllithium and triisopropyl borate.
Preparation of B-[2-(9H-carbazol-9-yl)phenyl]boronic acid
Preparation Report 1 of B-[2-(9H-carbazol-9-yl)phenyl]boronic acid,
①Synthesis of 9-(2-bromophenyl)-9H-carbazole (9-(2-bromophenyl)-9H-carbazole): carbazole (1eq) and o-bromoiodobenzene (3eq) cuprous iodide (0.05eq); add 11g of potassium carbonate (4eq) into a three-necked flask, add anhydrous N,N-dimethylformamide (DMF), and react at 140°C for 48h. After the reaction is completed, pour the reaction system into water , a large amount of solid precipitated, dissolved the solid with dichloromethane, mixed the sample, and passed through the column to obtain a white solid (47%); MS (APCI) (m/z): [M+H+]calcd, 322.2050; found, 322.2038
②Synthesis of B-[2-(9H-carbazol-9-yl)phenyl]boronic acid ((2-(9H-carbazol-9-yl)phenyl)boronicacid): 9-(2-bromophenyl) )-9H-carbazole (1eq), add dry tetrahydrofuran solution, cool to -78°C, replace N2 three times to ensure an oxygen-free environment of the system, add n-butyllithium ( 2.5M, 1.1eq), keep the reaction at -78°C for 1.5h, add triisopropyl borate (ρ=0.815g/ml, 1.1eq) dropwise, raise to room temperature after the dropwise addition, add diluted solution dropwise after 8h Quench the reaction with hydrochloric acid, remove tetrahydrofuran by distillation under reduced pressure, add dichloromethane to dissolve, wash with water, dry with anhydrous magnesium sulfate, filter, and recrystallize the filtrate to obtain a white solid product (90%).
Preparation Report 2 of B-[2-(9H-carbazol-9-yl)phenyl]boronic acid,
1) Add 7.80ml (71.8mmol) of 1-bromo-2-fluorobenzene to 10g (59.8mmol) of carbazole and 39.0g (120mmol) of cesium carbonate solution at 160°C, heat and stir After 16 hours, the reaction solution was cooled to room temperature, toluene was added, and insoluble matter was filtered off. The obtained solution was washed with water, dried over anhydrous sodium sulfate, purified by silica gel column chromatography, and the residue obtained from neodymium carbonate dihydrate was crystallized to obtain 18.3 g of the intermediate with a yield of 94%.
2) Under an argon atmosphere, dissolve 8.0g (24.8mmol) of the intermediate synthesized in step 1 in THF (124ml), cool it in a dry ice/acetone bath, and add 17.1ml (27.3mmol) of hexane dropwise Hexane solution and the mixture was stirred for 2 hours. Add 3.33 ml (29.8 mmol) of trimethyl borate dropwise, stir the mixture for 1 hour, remove the dry ice/acetone bath and allow the temperature to rise to room temperature. The reaction was cooled in an ice-water bath, 2M hydrochloric acid was added, the temperature was raised to room temperature, and the mixture was stirred for 1 hour, the obtained reaction solution was extracted with ethyl acetate, the organic layer was washed with water, dried over anhydrous sodium sulfate, and The obtained residue was concentrated under reduced pressure and crystallized to obtain 4.91 g of B-[2-(9H-carbazol-9-yl)phenyl]boronic acid in a yield of 69%.
References
[1]CN201710016833.0 A pyrimidine derivative and its application
[2] WO2018164239
