Methods of forming 4-chloro-2-fluoro-3-substituted-phenylboronic acid pinacol esters and methods of using the same

• Main Author: OPPENHEIMER JOSSIAN
• Format: Patent
• Language: English
• Published: 29.07.2016
• Subjects: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM; APPARATUS THEREFOR; CHEMISTRY; GENERAL METHODS OF ORGANIC CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

The disclosure relates to a method of using 4-chloro-2-fluoro-3-substituted-phenylboronic acid pinacol ester comprise reacting the ester with a Suzuki's coupling reactant in a medium consisting essentially of a palladium catalyst, a ligand, a base and at least one solvent to produce 6 (4-chloro-2-fluoro-3-substituted phenyl) 4 aminopicolinates. The disclosure also relates to a method of forming a 4-chloro-2-fluoro-3-substituted-phenylboronic acid pinacol ester, comprising: contacting a 1-chloro-3-fluoro-2-substituted benzene with an alkyl lithium to form a lithiated 1-chloro-3-fluoro-2-substituted benzene; contacting the lithiated 1-chloro-3-fluoro-2-substituted benzene with an electrophilic boronic acid derivative to form a 4-chloro-2-fluoro-3-substituted-phenylboronate; reacting the 4-chloro-2-fluoro-3-substituted-phenylboronate with an aqueous base to form a (4-chloro-2-fluoro-3-substituted-phenyl)trihydroxyborate; reacting the (4-chloro-2-fluoro-3-substituted-phenyl)trihydroxyborate with an acid to form a 4-chloro-2-fluoro-3-substituted-phenylboronic acid; and reacting the 4-chloro-2-fluoro-3-substituted-phenylboronic acid with 2,3-dimethyl-2,3-butanediol.