Process for the preparation of 4-amino-3-chloro-5-fluoro-6-(substituted) picolinates

A process for the preparation of a 4-amino-3-chloro-5-fluoro-6-(substituted)picolinate of the Formula I

• wherein
• R represents C1-C4 alkyl, cyclopropyl, C2-C4 alkenyl or phenyl substituted with from 1 to 4 substituents independently selected from halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy or C1-C4 haloalkoxy;
• R1 represents C1-C12 alkyl or an unsubstituted or substituted C7-C11 arylalkyl;
• which comprises the following steps:
• a) fluorinating 3,4,5,6-tetrachloropicolinonitrile (Formula A)
• with a source of fluoride ion to produce 3-chloro-4,5,6-trifluoropicolinonitrile (Formula B)
• b) aminating 3-chloro-4,5,6-trifluoro-2-picolinonitrile (Formula B) with ammonia to produce 4-amino-3-chloro-5,6-difluoropicolinonitrile (Formula C)
• c) exchanging the fluoro substituent in the 6-position of 4-amino-3-chloro-5,6-difluoropicolinonitrile (Formula C) with hydrogen bromide (HBr), hydrogen chloride (HC1) or hydrogen iodide (HI) and hydrolyzing the nitrile to produce a 4-amino-3-chloro-5-fluoro-6-halopicolinamide of Formula D
• wherein L is Br, Cl or I;
• d) esterifying the 4-amino-3-chloro-5-fluoro-6-halopicolinamide of Formula D with a strong acid and an alcohol (R1OH) to produce a 4-amino-3-chloro-5-fluoro-6-halopicolinate of Formula E
• wherein L and R1 are as previously defined;
• and
• e) coupling the 4-amino-3-chloro-5-fluoro-6-halopicolinate of Formula E with an aryl, alkyl or alkenyl metal compound of the Formula F
• R-Met F
• wherein R is as previously defined and Met represents Zn-halide, Zn-R, tri-(C1-C4 alkyl)tin, copper, or B(OR2OR3), where R2 and R3 are independent of one another, hydrogen, C1-C4 alkyl, or when taken together form an ethylene or propylene group in the presence of a transition metal catalyst to produce the 4-amino-3-chloro-5-fluoro-6-(substituted)picolinate of Formula I.