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

• US 8,871,943 B2
• Filed: 07/23/2013
• Issued: 10/28/2014
• Est. Priority Date: 07/24/2012
• Status: Active Grant

• Current Assignee: Corteva Agriscience LLC (Corteva, Inc.)
• Original Assignee: Dow Agrosciences LLC (Corteva, Inc.)
• Inventors: Renga, James M., Cheng, Yang, Muhuhi, Joseck M., Podhorez, David E., Roth, Gary A., West, Scott P., Whiteker, Gregory T., Zhu, Yuanming
• Primary Examiner(s): NORTHINGTON DAVIS, ZINNA
• Application Number:
  US13/949,060
• Publication Number:
  US 20140031556A1
• Time in Patent Office: 462 Days
• Field of Search: None
• US Class Current: 546/310
• CPC Class Codes: C07D 213/803 Processes of preparation

Abstract

Provided herein are processes for the preparation of 4-amino-5-fluoro-3-halo-6-(substituted)picolinates comprising a step of converting chloropicolinoyl chlorides to fluoropicolinoyl fluorides.

Claims

1. A process for preparing a compound of Formula (I):

2. The process of claim 1, 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.

3. The process of claim 1, wherein the transformation of a compound of Formula (III) to a compound of Formula (IV) comprises:

contacting the compound of Formula (III) with an alcohol R¹OH to form a compound of Formula (IX);

4. The process of claim 1, wherein the transformation of a compound of Formula (III) to a compound of Formula (IV) comprises:

contacting the compound of Formula (III) with an ammonia source to form a compound of Formula (X);

5. The process of claim 1, comprising:

transformation (a), which comprises;

(a-1) fluorinating a compound of Formula (A);

6. The process of claim 1, comprising:

transformation (a), which comprises;

(a-1) fluorinating a compound of Formula (A);

7. The process of claim 1, comprising:

transformation (c), which comprises;

coupling a compound of Formula (J);

8. The process of claim 1, comprising:

transformation (c), which comprises;

(c-1) coupling a compound of Formula (P);

9. The process of claim 1, further comprising protecting the NH₂ substituent in the 4-position of the pyridine structure prior to transformation (c);

and further comprising a deprotecting step.

10. The process of claim 1, wherein R is 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.

11. The process of claim 1, wherein an amine-containing compound of Formulas (I), (IV), (V), (VI), or (VIII) is purified by:

a) protonating with an acid to form a salt, b) isolating the salt in higher purity by crystallization, precipitation or extraction, and c) neutralizing the purified salt with a base to form the purified neutral amine-containing product or intermediate.

12. The process of claim 1, wherein the source of fluoride ion is a metal fluoride.

13. The process of claim 12, wherein the metal fluoride is selected from sodium fluoride, potassium fluoride and cesium fluoride.

14. The process of claim 13, wherein the metal fluoride is potassium fluoride.

15. The process of claim 1, wherein the fluorination step in transformation (a) occurs in the presence of a catalyst selected from a crown ether, a phosphonium halide, a polyether, a phosphazenium salt, and a tetra-substituted ammonium halide.

16. The process of claim 15, wherein the catalyst is a crown ether.

17. The process of claim 16, wherein the crown ether is 18-crown-6.

18. The process of claim 1, wherein the fluorination step in transformation (a) occurs in the presence of a solvent selected from an alkyl nitrile or an alkyl sulfone.

19. The process of claim 18, wherein the solvent is acetonitrile or sulfolane.

20. The process of claim 1, wherein the solvate is a hydrate.