Process for preparing halogenated pyridine derivatives

Patent metadata

Field	Value
Publication number	US-10766909-B2
Application number	US-201716312568-A
Country	US
Kind code	B2
Filing date	Jun 28, 2017
Priority date	Jul 5, 2016
Publication date	Sep 8, 2020
Grant date	Sep 8, 2020

Abstract

The present invention relates to a process for preparing halogenated pyridine derivatives of the formula (II) proceeding from compounds of the formula (I) via intermediates of the formula (IIIa) or (IIIb)

where the radicals
Q and W are each independently halogen, R 2 is halogen or —O-pivaloyl, and Y is halogen, CO 2 R 1 or NO 2 , where R 1 is (C 1 -C 6 )-alkyl or (C 1 -C 6 )-haloalkyl.

First claim

The invention claimed is:

1. A process for preparing a compound of formula (II)

wherein
Q and W are each independently halogen, and
Y is halogen, CO 2 R 1 or NO 2 , where R 1 is (C 1 -C 6 )-alkyl or (C 1 -C 6 )-haloalkyl,
wherein, in a first process step a), a compound of formula (I)

wherein W and Y each have the definitions given above,
is reacted with an organozinc base of structure (NR 3 R 4 )—Zn—R 2 or (NR 3 R 4 ) 2 —Zn wherein
R 2 is halogen or O-pivaloyl and
R 3 and R 4 together form a —(CH 2 ) 4 —, —(CH 2 ) 5 — or —(CH 2 ) 2 O(CH 2 ) 2 — group, where each of these groups may optionally be substituted by 1, 2, 3 or 4 R 5 radicals and R 5 is selected from the group consisting of methyl, ethyl, n-propyl and i-propyl,
to give a compound of formula (IIIa) or formula (IIIb)

wherein W, Y and R 2 each have the definitions given above,
wherein the step a) is conducted at a temperature between 30° C. and 80° C.,
and this compound of formula (IIIa) or (IIIb) is reacted in a second process step b) with a compound of the structure Q-X wherein X is halogen and Q has the abovementioned definition to give the compound of formula (II).

2. The process according to claim 1 , wherein
Q and X have the same definition and are each iodine or bromine,
W is fluorine or chlorine,
R 2 is halogen, and
Y is chlorine, bromine, CO 2 R 1 or NO 2 , where R 1 is (C 1 -C 4 )-alkyl.

3. The process according to claim 1 , wherein
R 3 and R 4 together form a —(CH 2 ) 5 — group, where each of these groups may optionally be substituted by 1, 2, 3 or 4 R 5 radicals, and
R 5 is selected from the group consisting of methyl and ethyl.

4. The process according to claim 1 , wherein
Q and X have the same definition and are each iodine,
W is fluorine,
R 2 is chlorine, and
Y is chlorine, bromine, CO 2 R 1 or NO 2 , where R 1 is methyl.

5. The process according to claim 1 , wherein
R 3 and R 4 together form a —(CH 2 ) 5 — group substituted by 4 methyl groups.

6. The process according to claim 1 , wherein the organozinc base is a compound of formula (V)
(TMP) x ZnCl 2-x ,  (V)

wherein x is the number 1 or 2.

7. The process according to claim 1 , wherein the organozinc base is present in conjunction with an alkali metal halide or alkaline earth metal halide.

8. The process according to claim 1 , wherein the organozinc base is used in a total amount of 0.5 to 5 equivalents, based on the compound of formula (I).

9. The process according to claim 1 , wherein the compound Q-X is an elemental halogen, optionally F 2 , Cl 2 , Br 2 or I 2 .

10. The process according to claim 1 , wherein the compound Q-X is used in a total amount of 0.5 to 10.0 equivalents, based on the compound of formula (I).

11. The process according to claim 1 , that is conducted in the presence of a solvent selected from the group consisting of tetrahydrofuran (THF), 1,4-dioxane, diethyl ether, diglyme, methyl tert-butyl ether (MTBE), tert-amyl methyl ether (TAME), 2-methyl-THF, toluene, xylenes, mesitylene, ethylene carbonate, propylene carbonate, N,N-dimethylacetamide, N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP), N-ethyl-2-pyrrolidone (NEP), N-butyl-2-pyrrolidone (NBP); N,N′-dimethylpropyleneurea (DMPU), halohydrocarbon, aromatic hydrocarbon, chlorohydrocarbon, tetrachloroethylene, tetrachloroethane, dichloropropane, methylene chloride, dichlorobutane, chloroform, carbon tetrachloride, trichloroethane, trichloroethylene, pentachloroethane, difluorobenzene, 1,2-dichloroethane, chlorobenzene, bromobenzene, dichlorobenzene, 1,2-dichlorobenzene, chlorotoluene, trichlorobenzene; 4-methoxybenzene, fluorinated aliphatic, fluorinated aromatic, trichlorotrifluoroethane, benzotrifluoride and 4-chlorobenzotrifluoride, or a mixture of at least two of these solvents with one another.

12. The process according to claim 11 , wherein the solvent is THF or N,N-dimethylformamide (DMF).

13. The process according to claim 1 , wherein step b) is conducted at a temperature between 0° C. and 80° C.

14. A compound of formula (IIIa)

wherein
W is fluorine,
Y is halogen, C(O) 2 R 1 or N(O) 2 , where R 1 is (C 1 -C 6 )-alkyl or (C 1 -C 6 )-haloalkyl, and
R 2 is halogen or O-pivaloyl.

15. A compound of formula (IIIb)

wherein
W is fluorine, and
Y is halogen, CO 2 R 1 or NO 2 , where R 1 is (C 1 -C 6 )-alkyl or (C 1 -C 6 )-haloalkyl.

16. A compound of formula (II)

wherein
Q is iodine,
W is fluorine, and
Y is Br, C(O) 2 R 1 or N(O) 2 , where R 1 is (C 1 -C 6 )-alkyl or (C 1 -C 6 )-haloalkyl.

17. The process according to claim 2 , wherein
R 2 is chlorine, bromine or iodine.

18. The process according to claim 7 , wherein the organozinc base is present in conjunction with lithium chloride or magnesium chloride.

19. The process according to claim 4 , wherein
Y is bromine.

Assignees

• Bayer Cropscience Ag

Inventors

• Mosrin Marc
• Fischer Ruediger
• Hager Dominik
• Hoffmeister Laura
• Kausch-Busies Nina
• Wilcke David
• Willot Matthieu

Classifications

• C07F3/06 Primary

  Zinc compounds · CPC title

• C07D213/803

  Processes of preparation · CPC title

• C07D213/79

  Acids; Esters · CPC title

• C07D213/61 Primary

  Halogen atoms or nitro radicals · CPC title