Process for synthesis of picolinamides

Patent metadata

Field	Value
Publication number	US-12281076-B2
Application number	US-202017754977-A
Country	US
Kind code	B2
Filing date	Oct 15, 2020
Priority date	Oct 18, 2019
Publication date	Apr 22, 2025
Grant date	Apr 22, 2025

Abstract

The present technology relates to processes, mixtures and intermediates useful for making picolinamide fungicides. The picolinamide compounds are prepared by processes that include coupling together a 4-methoxy-3-acyloxypicolinic acid with key 2-amino-L-alaninate esters derived from substituted 2-phenylethanols.

First claim

We claim:

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

wherein Z is CH 3 CO, CH 3 CH 2 CO or (CH 3 ) 2 CHCO;
from the compound of Formula B

wherein Z is CH 3 CO, CH 3 CH 2 CO or (CH 3 ) 2 CHCO;
which comprises the steps of:
a) creating a first mixture containing the compound of Formula B, wherein Z is CH 3 CO, CH 3 CH 2 CO or (CH 3 ) 2 CHCO, a coupling reagent, and a base;
b) adding at least one of the compounds of Formula C and Formula C1

wherein X is CI, Br, HSO 4 , H 2 PO 4 or CH 3 SO 3 ; 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 coupling reagent is an alkyl chloroformate of the Formula ClCO 2 R, wherein R is a C1-C4 alkyl or benzyl, or an acid chloride of the Formula RCOCl, wherein R is a C1-C4 alkyl.

3. 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.

4. 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.

5. The process of claim 1 wherein Z is CH 3 CH 2 CO.

6. The process of claim 1 wherein Z is CH 3 CO.

7. The process of claim 1 wherein Z is (CH 3 ) 2 CHCO.

8. The process of claim 1 wherein X is Cl.

9. The process of claim 1 wherein X is Br.

10. A process for the preparation of the compound of Formula C1:

wherein X is CI, Br, HSO 4 , H 2 PO 4 or CH 3 SO 3 ; comprising:
a) creating a first mixture containing the compound of Formula G2 as predominantly a single enantiomer

o-tolylmagnesium halide, and a copper catalyst;

b) isolating the compound of Formula D2

from the first mixture;

c) creating a second mixture containing the compound of Formula D2,

N-(tert-butoxycarbonyl)-L-alanine, an acylating agent, a catalyst and optionally a base;
d) isolating the compound of Formula F

from the second mixture;

e) creating a third mixture containing the compound of Formula F and a strong acid;
wherein the strong acid is HCl, HBr, HI, H 2 SO 4 , H 3 PO 4 , CF 3 COOH, or CH 3 SO 3 H; and

f) isolating the compound of Formula C1, wherein X is CI, Br, HSO 4 , H 2 PO 4 or CH 3 SO 3 , from the third mixture.

11. A process for the preparation of a compound of Formula B

wherein Z is CH 3 CH 2 CO;
comprising the steps of:
a) reacting a compound of Formula B, wherein Z is H with an acylating reagent, and a base; and
b) isolating the compound of Formula B, wherein Z is CH 3 CH 2 CO, from the mixture.

12. The process of claim 11 wherein the acylating agent is selected from one of propionic anhydride and propionyl chloride or mixtures thereof.

13. The compound of Formula B,

wherein Z is CH 3 CH 2 CO.

Assignees

• Corteva Agriscience Llc

Inventors

• Babij Nicholas R
• Mccusker Elizabeth O
• Whiteker Gregory T
• Sane Neeraj
• Tu Siyu
• Li Xiaoyong
• Klosowski Daniel W
• Mcgough Patrick T
• Guo Meng
• Robinson Matthew
• Nissen Jeffrey Scott
• Davis Tyler
• Hao Yan

Classifications

• C07C227/20

  by hydrolysis of N-acylated amino-acids or derivatives thereof, e.g. hydrolysis of carbamates · CPC title

• C07D213/803 Primary

  Processes of preparation · CPC title

• C07D213/79

  Acids; Esters · CPC title

• C07C269/06

  by reactions not involving the formation of carbamate groups · CPC title

• C07C29/36

  increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal · CPC title