Preparation of (3-(carbazol-9-yl)phenyl)pinacol borate ester_Industrial additives

Background and overview^[1]

(3-(Carbazol-9-yl)phenyl)pinacol borate can be used as a pharmaceutical synthesis intermediate. If (3-(carbazol-9-yl)phenyl)pinacol borate is inhaled, move the patient to fresh air; if skin contact occurs, remove contaminated clothing and rinse thoroughly with soap and water. If you feel discomfort on your skin, seek medical attention; if it comes into contact with your eyes, separate your eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse your mouth immediately, do not induce vomiting, and seek medical attention immediately. Cabot

Structure

Preparation ^[1-2]

The preparation of (3-(carbazol-9-yl)phenyl)pinacol borate is divided into the following two steps:

Step 1, preparation of 9-(3-bromophenyl)carbazole:

Under nitrogen protection, add copper iodide (135 mg, 0.71 mmol) to 1,10-phenanthroline (128 mg, 0.71 mmol), carbazole (2.36 g, 14.14 mmol), m-bromoiodobenzene ( 4g, 14.14mmol) and anhydrous potassium carbonate (3.9g, 28.28mmol) in DMF (20mL), and then the reaction was heated to 110-120°C and stirred overnight. After the reaction was cooled to room temperature, distilled water and methylene chloride were added to the reaction mixture. After liquid separation, the aqueous layer was extracted three times with methylene chloride. The organic layer was washed three times with distilled water, dried over anhydrous magnesium sulfate, filtered, distilled under reduced pressure to remove the solvent, and then separated using a silica gel column. The eluent was petroleum ether to obtain a white solid with a yield of 72% (3.3g).

Step 2, preparation of 9-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbazole:

Under nitrogen protection, dissolve 9-(3-bromophenyl)carbazole (1.5g, 4.66mmol) into anhydrous tetrahydrofuran (100mL), cool to -78°C, and slowly add n-butyl through a syringe. Lithium solution (2.05 mL, 2.5 M, 5.13 mmol) was maintained at this temperature for 15 to 30 minutes, and then isopropoxy pinacol borate (1.24 mL) was added.��6.06mmol); the reaction system slowly returned to room temperature and stirred overnight under N ₂ atmosphere. After the reaction is completed, add 2 mL of ethanol to terminate the reaction, and distill the solvent under reduced pressure. Add methylene chloride and distilled water for extraction. The organic layer is dried with anhydrous magnesium sulfate, filtered, and the solvent is distilled under reduced pressure. Then, it is separated with a silica gel column and eluted. The solvents were petroleum ether and methylene chloride, and a white solid was obtained with a yield of 84% (1.45g).

Application

(3-(Carbazol-9-yl)phenyl)pinacol borate can be used as a pharmaceutical synthesis intermediate. For example, prepare compound Phen-m-PhCz:

The specific steps are: under nitrogen protection, add palladium acetate (11mg, 0.05mmol) and tricyclohexylphosphine (28mg, 0.1mmol) to 3-bromo-1,10-phenanthroline (638mg, 2.46mmol) ), 9-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbazole (1g, 2.71mmol), In a mixed solution of potassium carbonate aqueous solution (3 mL, 2 M), ethanol (20 mL), and toluene (20 mL), the reaction was heated to 90-110°C and stirred overnight. After cooling to room temperature, distilled water was added to the reaction mixture and the toluene layer was separated, and the water layer was extracted three times with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure and then separated using a silica gel column. The eluent was dichloromethane and ethyl acetate to obtain a white solid with a yield of 90% (930 mg).

Main reference materials

[1] CN105646488 1,10-phenanthroline monohydrate-based main material and preparation method as well as application thereof