Processes for the preparation of 4-alkoxy-3-hydroxypicolinic acids
4-Alkoxy-3-hydroxypicolinic acids may be conveniently prepared from 4,6-dibromo-3-hydroxypicolinonitrile in a series of chemical steps selected from bromo substitution, nitrile hydrolysis and halogen reduction that are conducted as a single pot process. 4,6-Dibromo-3-hydroxypicolinonitrile may be prepared from furfural in a series of chemical steps selected from cyano-amination, amine salt formation and bromination-rearrangement.
1. A process for the preparation of a compound of Formula A
wherein R 1 is a C 1 -C 3 alkyl;
from a compound of Formula B
which comprises the following steps:
a) creating a first mixture containing an alkali metal alkoxide of Formula C
MOR 1 C
wherein M is Na or K, and R 1 is C 1 -C 3 alkyl;
and the compound of Formula B and heating the first mixture;
b) creating a second mixture by adding water, a strong base, and zinc metal to the first mixture;
c) heating the second mixture; and
d) isolating the compound of Formula A;
wherein the process further comprises removing zinc salts or zinc metal from the second mixture prior to heating the second mixture.
2. The process of claim 1 wherein M is Na and R 1 is methyl.
3. The process of claim 1 wherein the first mixture further comprises a solvent selected from the group consisting of: DMSO, methanol, sulfolane, and mixtures thereof.
4. The process of claim 1 wherein the strong base is selected from sodium hydroxide or potassium hydroxide.