B-(4-Chloro-3-methoxyphenyl)boronic acid

To 4-bromo-1-chloro-2-methoxybenzene (2.2 g, 9.9 mmol) in toluene/THF (16/6 mL) at -78° C. was added n-butyl lithium (8.7 mL, 1.6 M in hexane, 14 mmol) dropwise. The reaction was stirred at -78° C. for 30 min, then trimethylborate (2.2 mL, 19.8 mmol) was added. The reaction was allowed to warm to rt and stirred overnight and then quenched with 1 M HCl (15 mL). The organic layer was separated and dried over sodium sulfate. The solvent was removed and the crude product was purified by flash column chromatography to give 25A (1.2 g, 65percent yield) as a white solid. To 4-bromo-1-chloro-2-methoxybenzene (2.2 g, 9.9 mmol) in toluene/THF (16/6 mL) at -78° C. was added n-butyl lithium (8.7 mL, 1.6 M in hexane, 14 mmol) dropwise. The reaction was stirred at -78° C. for 30 min., then trimethylborate (2.2 mL, 19.8 mmol) was added. The reaction was allowed to warm to rt and stirred overnight and then quenched with 1 M HCl (15 mL). The organic layer was separated and dried over sodium sulfate. The solvent was removed and the crude product was purified by flash column chromatography to give 79A (1.2 g, 65percent yield) as a white solid. To a stuffed solution of 4-bromo-i-chloro-2-methoxybenzene (2 g, 9.03 mmol) in diethyl ether (20 mL) was added n-BuLi (2 M in hexane; 5.2 mL, 10.4 mmol) at -78 °C dropwise. The reaction was allowed to stir at -78 °C for 30 mm, and then triisopropyl borate (2.4 mL, 10.40 mmol) was slowly added to the reaction mixture at -78 °C. The temperature of the reaction mixture was gradually raised to RT over a period of 1 h, and then the reaction was stirred at RT for 30 mm. After 30 mm, 3 N HC1 (100 mL) was slowly added to the reaction mixture at 0 °C and the reaction was stirred for further 1 h. The progress of reaction was monitored by TLC. After completion of reaction, the reaction mixture was extracted with EtOAc (2x200 mL). The combined organic layers were washed with brine (100 mL), dried over sodium sulfate and concentrated to obtain a crude product. The residue obtained was triturated with hexane (2x25 mL) to afford 4-chloro-3-methoxyphenylboronic acid (900 mg) as a white solid.5-bromo-2-chloro anisole (leq) in toluene (8vol) and THF (3vol) at -78oC was added n-BuLi (1.5eq) drop wise. The resulting mixture was stirred at -78oC for 30 minutes under an atmosphere of N2.Trimethylborate (2eq) was then added to the reaction mixture and this was allowed to warm to room temperature and stirred for 16 hours. The reaction mixture was quenched with 1M HC1 and the organic layer was separated. The organic layer was washed with saturated aqueous NaCl (20vol), dried over Na2S04, filtered and the solvent removed in vacuum. The resulting residue was purified by flash column chromatography (eluent:[1 : 1] EtOAc: heptane) to afford the required target compound (1.15g, 31percent).

Molecular Weight:186.40
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:186.0255020
Monoisotopic Mass:186.0255020
Topological Polar Surface Area:49.7
Heavy Atom Count:12
Complexity:145
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes