944129-07-1Relevant articles and documents
Design and application of a low-temperature continuous flow chemistry platform
Newby, James A.,Blaylock, D. Wayne,Witt, Paul M.,Pastre, Julio C.,Zacharova, Marija K.,Ley, Steven V.,Browne, Duncan L.
, p. 1211 - 1220 (2014/12/10)
A flow reactor platform technology applicable to a broad range of low temperature chemistry is reported. The newly developed system captures the essence of running low temperature reactions in batch and represents this as a series of five flow coils, each with independently variable volume. The system was initially applied to the functionalization of alkynes, Grignard addition reactions, heterocycle functionalization, and heteroatom acetylation. This new platform has then been used in the preparation of a 20-compound library of polysubstituted, fluorine-containing aromatic substrates from a sequential metalation-quench procedure and can be readily adapted to provide gaseous electrophile inputs such as carbon dioxide using a tube-in-tube reactor.
METHODS OF PRODUCING METHYL 4-AMINO-3-CHLORO-6-(4-CHLORO-2-FLUORO-3-METHOXYPHENYL)PYRIDINE-2-CARBOXYLATE
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Page/Page column 15, (2013/07/19)
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 AND SYSTEMS FOR FORMING BORONIC ACIDS AND INTERMEDIATES THEREOF
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Paragraph 0045, (2013/03/28)
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 OF FORMING 4-CHLORO-2-FLUORO-3-SUBSTITUTED-PHENYLBORONIC ACID PINACOL ESTERS AND METHODS OF USING THE SAME
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Page/Page column 10-11, (2013/07/19)
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.
METHODS OF ISOLATING 4-CHLORO-2-FLUORO-3-SUBSTITUTED-PHENYLBORONIC ACIDS
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Page/Page column 12, (2013/03/26)
Provided herein are methods of isolating a 4-chloro-2-fluoro-3-substituted-phenylboronic acid. The method comprises contacting a mixture of water, a water miscible organic solvent, and a 4-chloro-2-fluoro-3-substituted-phenylboronic acid with a salt to form a water miscible organic solvent layer and a water layer. The 4-chloro-2-fluoro-3-substituted-phenylboronic acid is partitioned into the water miscible organic solvent layer, which is separated from the water layer. Additional methods are disclosed, as is a 4-chloro-2-fluoro-3-substituted-phenylboronic acid produced by one of the methods, wherein the 4-chloro-2-fluoro-3-substituted-phenylboronic acid is obtained at a yield of greater than approximately 90%.
PROCESS FOR THE SELECTIVE DEPROTONATION AND FUNCTIONALIZATION OF 1-FLUORO-2-SUBSTITUTED-3-CHLOROBENZENES
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Page/Page column 2, (2009/07/25)
1-Fluoro-2-substituted-3-chlorobenzenes are selectively deprotonated and functionalized in the position adjacent to the fluoro substituent.
