Dow Agrosciences LLC

Mark V M Emonds

Jossian Oppenheimer

James M Renga

Thomas L Siddall

Kim Eric Arndt

Karl L Krumel

Mark W Zettler

Christopher W Derstine

Robert C Clouse

Catherine A Menning

Jennifer M Schomaker

D Wayne Blaylock

Methods for forming boronic acids, and intermediates thereof, are disclosed. The method may include mixing a 1-chloro-2-substituted-3-fluorobenzene starting material with an alkyllithium in a first reactor to form a reaction mixture. The 1-chloro-2-substituted-3-fluorobenzene starting material may react with the alkyllithium to form a lithiated intermediate. The reaction mixture may be continuously transferred to a second reactor and a borate may be continuously introduced to form a boronate. The boronic acids may be formed by treating the boronate with aqueous potassium hydroxide followed by acidification. Such methods may provide continuous formation of the boronic acids and may reduce an amount of a reactive intermediate present during processing as well as cycle times. Systems for forming the boronic acids are also disclosed.

Methods and systems for forming boronic acids and intermediates thereof

Methods of producing methyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)pyridine-2-carboxylate. One method comprises adding methyl isobutyl ketone to an aqueous solution comprising 4-chloro-2-fluoro-3-methoxyphenyl-boronic acid to form an organic phase comprising the 4-chloro-2-fluoro-3-methoxyphenylboronic acid and an aqueous phase. The organic phase and the aqueous phase are separated. The 4-chloro-2-fluoro-3-methoxyphenylboronic acid is reacted with methyl 4-(acetylamino)-3,6-dichloropyridine-2-carboxylate in methyl isobutyl ketone to produce methyl 4-(acetylamino)-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)pyridine-2-carboxylate, which is deacetylated to produce methyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)pyridine-2-carboxylate.

Methods of producing methyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)pyridine-2-carboxylate

1-Fluoro-2-substituted-3-chlorobenzenes are selectively deprotonated and functionalized in the position adjacent to the fluoro substituent.

Process for the selective deprotonation and functionalization of 1-fluoro-2-substituted-3-chlorobenzenes

1-Halo-2-chloro-3-alkoxy-4-alkylsulfonylbenzene and 1-halo-2,3-dichloro-4-alkylsulfonylbenzene compounds were converted to compounds having hydroxycarbonyl or alkoxycarbonyl substituents in place of the 1-halo substituent by reaction with carbon monoxide and water or an alcohol respectively, in the presence of a palladium II salt: trihydrocarbylphosphine complex type catalyst.

Process for preparing 2-chloro-3-alkoxy-4-alkylsulfonyl-benzoic acids and esters

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Midland, MI, United States of America

Mark V M Emonds