Methods of isolating (4-chloro-2-fluoro-3-substituted-phenyl)boronates and methods of using the same

A method of synthesizing and isolating dimethyl 4-chloro-2-fluoro-3-methoxyphenylboronate, comprising:

• contacting a solution comprising 2-chloro-6-fluoroanisole and 1,2-dimethoxyethane with n-butyl lithium to form a reaction mixture comprising 6-chloro-2-fluoro-3-lithioanisole and the 1,2-dimethoxyethane;
• contacting the reaction mixture with trimethyl borate to form a salinated phenyl boronate solution comprising dimethyl 4-chloro-2-fluoro-3-methoxyphenylboronate, the 1,2-dimethoxyethane, and at least one lithium salt;
• introducing carbon dioxide gas or carbon dioxide solid (dry ice) to the salinated phenyl boronate solution to form a mixture comprising the dimethyl 4-chloro-2-fluoro-3-methoxyphenylboronate, the 1,2-dimethoxyethane, and lithium methyl carbonate;
• and
• separating the lithium methyl carbonate to form a desalinated phenyl boronate solution comprising the dimethyl 4-chloro-2-fluoro-3-methoxyphenylboronate and the 1,2-dimethoxyethane.

A 4-chloro-2-fluoro-3-substituted-phenylboronate produced by a process comprising:

• adding carbon dioxide gas or carbon dioxide solid (dry ice) to a solution comprising a 4-chloro-2-fluoro-3-substituted-phenylboronate, an inert organic solvent, and at least one lithium salt to react the at least one lithium salt with the carbon dioxide gas and form a mixture comprising the 4-chloro-2-fluoro-3-substituted-phenylboronate, the inert organic solvent, and a precipitated solid;
• and
• removing the precipitated solid from the mixture;
• wherein the 4-chloro-2-fluoro-3-substituted-phenylboronate is obtained at a yield of greater than or equal to about 90%.