# US 10,766,909 B2 · Process for preparing halogenated pyridine derivatives > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,766,909 B2 - Document ID: US10766909B2 - Status: Granted - Kind: B2 - Application number: 16/312,568 - Filed: 2017-06-28 - Published: 2019-10-31 - Granted: 2020-09-08 - Earliest claimed: 2016-07-05 - Assignees: Bayer CropScience AG - Applicants: Bayer CropScience Aktiengesellschaft - Inventors: Marc Mosrin; Ruediger Fischer; Dominik Hager; Laura Hoffmeister; Nina Kausch-Busies; David Wilcke; Matthieu Willot - Web page: https://patentgrep.com/patent/US10766909B2 ## CPC - C07D 213/61: Halogen atoms or nitro radicals - C07F 3/06: Zinc compounds - C07D 213/79: Acids; Esters - C07D 213/803: Processes of preparation - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22) ## 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, R2 is halogen or —O-pivaloyl, and Y is halogen, CO2R1 or NO2, where R1 is (C1-C6)-alkyl or (C1-C6)-haloalkyl. ## Claims ### Claim 1 A process for preparing a compound of formula (II) wherein Q and W are each independently halogen, and Y is halogen, CO2R1 or NO2, where R1 is (C1-C6)-alkyl or (C1-C6)-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 (NR3R4)—Zn—R2 or (NR3R4)2—Zn wherein R2 is halogen or O-pivaloyl and R3 and R4 together form a —(CH2)4—, —(CH2)5— or —(CH2)2O(CH2)2— group, where each of these groups may optionally be substituted by 1, 2, 3 or 4 R5 radicals and R5 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 R2 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). ### Claim 2 (depends on 1) 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, R2 is halogen, and Y is chlorine, bromine, CO2R1 or NO2, where R1 is (C1-C4)-alkyl. ### Claim 3 (depends on 1) The process according to claim 1, wherein R3 and R4 together form a —(CH2)5— group, where each of these groups may optionally be substituted by 1, 2, 3 or 4 R5 radicals, and R5 is selected from the group consisting of methyl and ethyl. ### Claim 4 (depends on 1) The process according to claim 1, wherein Q and X have the same definition and are each iodine, W is fluorine, R2 is chlorine, and Y is chlorine, bromine, CO2R1 or NO2, where R1 is methyl. ### Claim 5 (depends on 1) The process according to claim 1, wherein R3 and R4 together form a —(CH2)5— group substituted by 4 methyl groups. ### Claim 6 (depends on 1) The process according to claim 1, wherein the organozinc base is a compound of formula (V) (TMP)xZnCl2-x, (V) wherein x is the number 1 or 2. ### Claim 7 (depends on 1) The process according to claim 1, wherein the organozinc base is present in conjunction with an alkali metal halide or alkaline earth metal halide. ### Claim 8 (depends on 1) 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). ### Claim 9 (depends on 1) The process according to claim 1, wherein the compound Q-X is an elemental halogen, optionally F2, Cl2, Br2 or I2. ### Claim 10 (depends on 1) 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). ### Claim 11 (depends on 1) 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. ### Claim 12 (depends on 11) The process according to claim 11, wherein the solvent is THF or N,N-dimethylformamide (DMF). ### Claim 13 (depends on 1) The process according to claim 1, wherein step b) is conducted at a temperature between 0° C. and 80° C. ### Claim 14 A compound of formula (IIIa) wherein W is fluorine, Y is halogen, C(O)2R1 or N(O)2, where R1 is (C1-C6)-alkyl or (C1-C6)-haloalkyl, and R2 is halogen or O-pivaloyl. ### Claim 15 A compound of formula (IIIb) wherein W is fluorine, and Y is halogen, CO2R1 or NO2, where R1 is (C1-C6)-alkyl or (C1-C6)-haloalkyl. ### Claim 16 A compound of formula (II) wherein Q is iodine, W is fluorine, and Y is Br, C(O)2R1 or N(O)2, where R1 is (C1-C6)-alkyl or (C1-C6)-haloalkyl. ### Claim 17 (depends on 2) The process according to claim 2, wherein R2 is chlorine, bromine or iodine. ### Claim 18 (depends on 7) The process according to claim 7, wherein the organozinc base is present in conjunction with lithium chloride or magnesium chloride. ### Claim 19 (depends on 4) The process according to claim 4, wherein Y is bromine.