3-CHLORO-2-FLUOROPHENYLBORONIC ACID

In a 500-mL three-neck flask was put 16 g (72 mmol) of1-bromo-3-chloro-2-fluorobenzene, and the air in the flask was replaced with nitrogen;15 then, 200 mL oftetrahydrofuran was added and the solution was cooled down to -80 ocunder a nitrogen stream. To this solution, 48 mL (76 mmol) of n-butyl lithium (a 1.6moi/L hexane solution) was added dropwise with a syringe, and then the mixture wasstirred for 1.5 hours at the same temperature. After stirring, 9.0 mL (80 mmol) oftrimethyl borate was added to this mixture. While the temperature was raised to room20 temperature, the mixture was stirred for about 19 hours. After stirring, about 100 mL of a I moi/L hydrochloric acid was added to the resulting solution and the mixture wasstirred. The organic layer of this mixture was washed with water and the aqueouslayer was subjected to extraction with toluene twice. The solution of the extract andthe organic layer were combined and washed with a saturated aqueous solution of5 sodium chloride. The resulting organic layer was dried over magnesium sulfate, andthis mixture was gravity-filtered. The resulting filtrate was concentrated to give 4.5 gof a pale yellow solid of a target substance, in a yield of 35 percent.Into a 500 mL three-neck flask was put 16 g (72 mmol) of 1-bromo-3-chloro-2-fluorobenzene, and the air in the flask was replaced with nitrogen.After that, 200 mL of tetrahydrofuran was added to the solution, and this mixture solution was cooled down to —80 °C. To this mixture solution, 48 mL (76 mmol) of n-BuLi (a 1.6 mol/L hexane solution) was dropped with a syringe, and then the resulting mixture was stirred at —80 °C for 1.5 hours.After stirring, 9.0 mL (80 mmol) of trimethyl borate was added to this mixture. The mixture was stirred for approximately 19 hours while the temperature of the mixture was being returned to room temperature. After the stirring, approximately 100 mL of a 1 mol/L hydrochloric acid was added to the obtained solution, and the mixture was stirred. An organic layer of this mixture was washed with water and an aqueouslayer was subjected to extraction with toluene twice. The extracted solution and the organic layer were combined and washed with saturated saline. The obtained organic layer was dried with magnesium sulfate, and this mixture was gravity-filtered. The obtained filtrate was concentrated to give 4.5 g of a pale yellow solid of the target substance in 35 percent yield. A synthesis scheme of Step 1 is shown in (c—i).

Molecular Weight:174.37
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:174.0055154
Monoisotopic Mass:174.0055154
Topological Polar Surface Area:40.5
Heavy Atom Count:11
Complexity:136
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes