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

摘要

The disclosure relates to a method of producing methyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxy-phenyl)pyridine-2-carboxy late, comprising: adding methyl isobutyl ketone to an aqueous solution comprising 4-chloro-2-fluoro-3-methoxy-phenylboronic acid to form an organic phase comprising the 4-chloro-2-fluoro-3-methoxy-phenylboronic acid and an aqueous phase; separating the organic phase comprising the 4-chloro-2-fluoro-3-methoxyphenylboronic acid from the aqueous phase; reacting the 4-chloro-2-fluoro-3-methoxyphenylboronic acid with methyl 4-(acetylamino)-3,6-dichloropyridine-2-carboxylate in methyl isobutyl ketone in the presence of a palladium catalyst and a ligand to produce methyl 4-(acetylamino)-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)pyridine-2-carboxylate; and deacetylating the methyl 4-(acetylamino)-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)pyridine-2-carboxylate to produce methy14-amino-3-chloro-6-(4-chloro-2-fluoro-3 -methoxypheny l)pyridine-2-carboxylate.