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

Patent metadata

Field	Value
Publication number	US-9598368-B2
Application number	US-201314049645-A
Country	US
Kind code	B2
Filing date	Oct 9, 2013
Priority date	Jan 25, 2011
Publication date	Mar 21, 2017
Grant date	Mar 21, 2017

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.

First claim

What is claimed is:

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

wherein
R represents C 1 -C 4 alkyl, cyclopropyl, C 2 -C 4 alkenyl or phenyl substituted with from 1 to 4 substituents independently selected from halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy or C 1 -C 4 haloalkoxy; and
R 1 represents C 1 -C 12 alkyl or an unsubstituted or substituted C 7 -C 11 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 (R 1 OH) to produce a 4-amino-3-chloro-5-fluoro-6-halopicolinate of Formula F

wherein L and R 1 , 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-(C 1 -C 4 alkyl)tin, copper, or B(OR 2 )(OR 3 ), where R 2 and R 3 are independent of one another, hydrogen, C 1 -C 4 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.

2. The process of claim 1 in which the coupling of step f) is performed prior to the hydrolysis and esterification of step e).

3. 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).

Assignees

• Zhu Yuanming
• Whiteker Gregory T
• Arndt Cynthia
• Renga James M
• Froese Robert D J
• Dow Agrosciences Llc

Inventors

• Zhu Yuanming
• Whiteker Gregory T
• Arndt Kim E
• Renga James M
• Froese Robert D J

Classifications

• C07D213/803

  Processes of preparation · CPC title

• C07D213/807 Primary

  by oxidation of pyridines or condensed pyridines · CPC title

• C07D213/79

  Acids; Esters · CPC title

• C07D213/84 Primary

  Nitriles · CPC title

• C07D213/89

  with hetero atoms directly attached to the ring nitrogen atom · CPC title