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US 9,598,368 B2Granted
Process for the preparation of 4-amino-3-chloro-5-fluoro-6-(substituted)picolinates
AssigneeDow AgroSciences LLC
InventorsYuanming Zhu, Gregory T. Whiteker, Kim E. Arndt, James M. Renga, Robert D. J. Froese
Life of this patent
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Abstract
4-Amino-3-chloro-5-fluoro-6-(substituted)picolinates are conveniently prepared from 3,4,5,6-tetrachloropicolinonitrile by a series of steps involving fluorine exchange, amination, reaction with hydrazine, halogenation, hydrolysis and esterification, and transition metal assisted coupling.
Claims3
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;
- and
- 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-trifluoropicolinonitrile (Formula B) with ammonia to produce 4-amino-3-chloro-5,6-difluoropicolinonitrile (Formula C)
- c) reacting the fluoro substituent in the 6-position of 4-amino-3-chloro-5,6-difluoropicolinonitrile (Formula C) with hydrazine to produce 4-amino-3-chloro-5-fluoro-6-hydrazinopicolinonitrile (Formula D)
- d) halogenating 4-amino-3-chloro-5-fluoro-6-hydrazinopicolinonitrile (Formula D) with a chlorine, bromine or iodine source to produce a 4-amino-3-chloro-5-fluoro-6-halopicolinonitrile of Formula E
- wherein L is Br, Cl or I;
- e) hydrolyzing and esterifying the 4-amino-3-chloro-5-fluoro-6-halopicolinonitrile of Formula E with a strong acid and an alcohol (R1OH) to produce a 4-amino-3-chloro-5-fluoro-6-halopicolinate of Formula F
- wherein L and R1, are as previously defined;
- and
- f) coupling the 4-amino-3-chloro-5-fluoro-6-halopicolinate of Formula F with an aryl, alkyl or alkenyl metal compound of the Formula G
- R-Met G
- wherein R is as previously defined and Met represents, Zn-halide, Zn—R, tri-(C1-C4 alkyl)tin, copper, or B(OR2)(OR3), 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.
14 more elements
An improved process of increasing the amount of recoverable 3-chloro-4,5,6-trifluoropicolinonitrile (Formula B)
- prepared from fluorinating 3,4,5,6-tetrachloropicolinonitrile (Formula A)
- with a source of fluoride ion wherein the improvement comprises the steps of:
- i) isolating the over-fluorinated 3,4,5,6-tetrafluoropicolinonitrile (H)
- by-product from fluorinating 3,4,5,6-tetrachloropicolinonitrile;
- ii) reacting the isolated 3,4,5,6-tetrafluoropicolinonitrile (H) (a) with lithium chloride (LiCl), (b) with 3,4,5,6-tetrachloropicolinonitrile (Formula A) in the presence of a phase-transfer catalyst or (c) with a combination of LiCl and 3,4,5,6-tetrachloropicolinonitrile to produce a mixture consisting predominantly of 3,4,5,6-tetrachloropicolinonitrile, monofluoro-trichloropicolinonitrile and difluoro-dichloropicolinonitrile;
- and
- iii) recycling the mixture consisting predominantly of 3,4,5,6-tetrachloropicolinonitrile, monofluoro-trichloropicolinonitrile and difluoro-dichloropicolinonitriles to the fluorination reaction preparing 3-chloro-4,5,6-trifluoropicolinonitrile (Formula B).
4 more elements
Dependencies are inferred from the claim text.