Processes for the preparation of 4-alkoxy-3-(acyl or alkyl)oxypicolinamdes

Patent metadata

Field	Value
Publication number	US-10358423-B2
Application number	US-201816035738-A
Country	US
Kind code	B2
Filing date	Jul 16, 2018
Priority date	Jul 7, 2016
Publication date	Jul 23, 2019
Grant date	Jul 23, 2019

Abstract

A fungicidal 4-methoxy-3-acetyloxypicolinamide may be conveniently prepared in processes that include the coupling together of 4-methoxy-3-acetyloxypicolinic acid or 4-methoxy-3-hydroxypicolinic acid with a key 2-aminopropanoate ester derived from a 1,1-bis(4-fluorophenyl)propane-1,2-diol.

First claim

What is claimed is:

1. A process for the preparation of the compound of Formula A

wherein Y is CH 3 CO;

from the compound of Formula B

which comprises the following steps:
a) creating a first mixture containing the compound of Formula B, an acylating agent or a chlorinating agent, and a base;
b) adding at least one of the compounds of Formula C and Formula J

wherein X is Cl, Br, HSO 4 , H 2 PO 4 or CH 3 SO 3 and

to the first mixture to form a second mixture; and
c) isolating the compound of Formula A from the second mixture.

2. The process of claim 1 wherein the acylating agent is an alkyl chloroformate of the Formula ClCO 2 R, wherein R is a C 1 -C 4 alkyl or benzyl, or an acid chloride of the Formula RCOCl, wherein R is a C 1 -C 4 alkyl.

3. The process of claim 1 wherein the chlorinating agent is oxalyl chloride or thionyl chloride.

4. The process of claim 1 wherein the base may be selected from the group including triethylamine (TEA), diisopropylethylamine (DIPEA), pyridine, potassium carbonate, and mixtures thereof.

5. The process of claim 1 wherein the first mixture further comprises a solvent selected from the group including dichloromethane (DCM), 1,2-dichloroethane (DCE), isopropyl acetate, tetrahydrofuran (THF), 2-MeTHF, acetonitrile (ACN), and mixtures thereof.

6. A process for the preparation of the compound of Formula A

wherein Y is CH 3 CO or CH 3 COOCH 2 ,

which comprises the following steps:
a) creating a first mixture containing the compound of Formula D,

an acylating agent, and a first base;
b) adding at least one of the compounds of Formula C and Formula J

wherein X is Cl, Br, HSO 4 , H 2 PO 4 or CH 3 SO 3 and

to the first mixture to form a second mixture; and
c) isolating the compound of Formula E from the second mixture;

wherein R 1 is a C 1 -C 4 alkyl or a benzyl;

d) creating a third mixture containing the compound of Formula E, an alkali metal base and water;
e) isolating the compound of Formula F from the third mixture;

f) creating a fourth mixture containing the compound of Formula F, an acetylating agent or an alkylating agent, and a second base; and
g) isolating the compound of Formula A from the fourth mixture.

7. The process of claim 6 wherein the acylating agent is an alkyl chloroformate of the Formula ClCO 2 R, wherein R is a C 1 -C 4 alkyl or a benzyl.

8. The process of claim 6 wherein the first mixture further comprises a solvent selected from the group including dichloromethane (DCM), 1,2-dichloroethane (DCE), acetonitrile (ACN), isopropyl acetate, THF, 2-MeTHF, and mixtures thereof.

9. The process of claim 6 wherein the first base may be selected from the group including triethylamine (TEA), diisopropylethylamine (DIPEA), pyridine and potassium carbonate.

10. The process of claim 6 wherein about 3 equivalents of the first base and about 2 equivalents of the acylating agent are used.

11. The process of claim 6 wherein the alkali metal base may be selected from the group including LiOH, NaOH, KOH, and mixtures thereof.

12. The process of claim 6 wherein the third mixture further comprises a co-solvent selected from the group including THF, 2-MeTHF, DME, dioxane, ACN and a C 1 -C 4 alcohol.

13. The process of claim 6 wherein the acetylating agent may be selected from acetic anhydride and acetyl chloride.

14. The process of claim 6 wherein the alkylating agent is CH 3 COOCH 2 Br.

15. The process of claim 6 wherein the second base may be selected from the group including pyridine, TEA, DIPEA, and mixtures thereof.

Assignees

• Dow Agrosciences Llc

Inventors

• Whiteker Gregory T
• Choy Nakyen
• Borromeo Peter
• Babij Nicholas R
• Roth Gary
• Hanley Patrick S
• Ober Matthias S
• Staton Tina
• Knueppel Daniel I
• Wald Grant Von
• Hough Nicole

Classifications

• A61P31/10

  Antimycotics · CPC title

• C07C229/08 Primary

  the nitrogen atom of the amino group being further bound to hydrogen atoms · CPC title

• C07C227/18

  by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters · CPC title

• A01N37/44

  containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids · CPC title

• C07D213/81 Primary

  Amides; Imides · CPC title