Synthesis of 4-amino-6-(heterocyclic)picolinates

A process for the preparation of a 4-amino-6-(heterocyclic) picolinate of Formula I:

• wherein
• R represents H, C1-C12 alkyl, C3-C12 alkynyl, C1-C3 alkyl substituted with CN, or C6-C12 arylalkyl;
• W1 represents H or F;
• W2 represents H, F, C1, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, or C1-C3 haloalkoxy;
• Y represents H, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy;
• and
• Z represents C1-C4 alkyl, C1-C3 alkoxy, C1-C4 haloalkyl, C1-C3 haloalkoxy, C1-C3 alkoxy-substituted C1-C3 alkyl, or —NR1R2, wherein R1 and R2 are independently hydrogen, C1-C3 alkyl, or C1-C3 haloalkyl;
• and
• Y and Z taken together are a 5-membered aromatic or non-aromatic, heterocyclic ring;
• the process comprising the following steps:
• a. creating a first mixture containing a compound of Formula A,
• wherein
• R represents H, C1-C12 alkyl, C3-C12 alkynyl, C1-C3 alkyl substituted with CN, or C6-C12 arylalkyl;
• a compound of Formula B1 or Formula B2, or mixtures thereof,
• wherein
• M+ represents an alkali metal cation;
• R3 represents H or C1-C6 alkyl, or alternatively two R3 may form a C2-C6 alkyl linkage, which together with B and two O form a 5- to 9-atom cyclic structure;
• R4 represents C1-C6 alkyl;
• W1 represents H or F;
• W2 represents H, F, C1, C1-C4 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy or C1-C3 haloalkoxy;
• Y represents halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy;
• and
• Z represents C1-C4 alkyl, C1-C3 alkoxy, C1-C4 haloalkyl, C1-C3 haloalkoxy, C1-C3 alkoxy-substituted C1-C3 alkyl, or —NR1R2, wherein R1 and R2 are independently hydrogen, C1-C3 alkyl, or C1-C3 haloalkyl;
• and
• Y and Z taken together are a 5-membered aromatic or non-aromatic, heterocyclic ring;
• one or more bases;
• and one or more solvents;
• b. adding a palladium catalyst, and optionally a ligand to the first mixture to form a second mixture;
• and
• c. heating the second mixture to a temperature of between about 25° C. and about 100° C.