METHODS OF FORMING 4-CHLORO-2-FLUORO-3-SUBSTITUTED-PHENYLBORONIC ACID PINACOL ESTERS AND METHODS OF USING THE SAME

• Main Author: Jossian OPPENHEIMER
• Format: Patent
• Language: English; Spanish
• Published: 05.09.2016
• 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; METALLURGY; ORGANIC CHEMISTRY

Methods include formation of 4-chloro-2 fluoro-3 substituted-phenylboronic acid pinacol esters. The method comprises contacting a 1-chloro-3-fluoro-2-substituted benzene with an alkyl lithium to form a lithiated 1-chloro-3-fluoro-2-substituted benzene. The lithiated 1-chloro-3-fluoro-2-substituted benzene is contacted with an electrophilic boronic acid derivative to form a 4-chloro-2-fluoro-3-substituted-phenylboronate. The 4-chloro-2-fluoro-3-substituted-phenylboronate is reacted with an aqueous base to form a (4-chloro-2-fluoro-3-substituted phenyl)trihydroxyborate. The (-chloro-2-fluoro-3-substituted phenyl)trihydroxyborate is reacted with an acid to form a 4-chloro-2-fluoro-3-substituted phenylboronic acid. The 4-chloro-2-fluoro-3-substituted phenylboronic acid is reacted with 2,3 dimethyl 2,3 butanediol to form 4-chloro-2-fluoro-3-substituted phenylboronic acid pinacol esters. Methods of using 4-chloro-2-fluoro-3-substituted phenylboronic acid pinacol esters to produce 6 (4-chloro-2-fluoro-3-substituted phenyl) 4 aminopicolinates are also disclosed. Los métodos incluyen la formación de ésteres pinacólicos de ácido 4-cloro-2-fluoro-3-sustituido-fenilborónico. El método comprende poner en contacto un 1-cloro-3-fluoro-2-sustituido-benceno con un alquil-litio para formar un 1-cloro-3-fluoro-2-sustituido-benceno litiado. El 1-cloro-3-fluoro-2-sustituido-benceno litiado se pone en contacto con un derivado de ácido borónico electrofílico para formar un 4-cloro-2-fluoro-3-sustituido-fenilboronato. El 4-cloro-2-fluoro-3-sustituido-fenilboronato se hace reaccionar con una base acuosa para formar un (4-cloro-2-fluoro-3-sustituido- fenil)trihidroxiborato. El (4-cloro-2-fluoro-3-sustituido-fenil)tr ihidroxiborato se hace reaccionar con un ácido para formar un ácido 4-cloro-2-fluoro-3-sustituido-fenilborónico. El ácido 4-cloro-2-fluoro-3-sustituido-fenilborónico se hace reaccionar con 2,3-dimetil-2,3-butanodiol para formar ésteres pinacólicos de ácido 4-cloro-2-fluoro-3-sustituido-fenilborónico. Los métodos de uso de ésteres pinacálicos de ácido 4-cloro-2-fluoro-3-sustituido- fenilborónico para producir 6-(4-cloro-2-fluoro-3-sustituido-fenil )-4-aminopicolinatos también se describen.