Process for preparing halogenated pyridine derivatives

Patent metadata

Field	Value
Publication number	US-10875858-B2
Application number	US-201716325666-A
Country	US
Kind code	B2
Filing date	Aug 9, 2017
Priority date	Aug 16, 2016
Publication date	Dec 29, 2020
Grant date	Dec 29, 2020

Abstract

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

in which
Q is a structural element

where the symbol # indicates the bond to the rest of the molecule and A, Q 1 , Q 2 , Q 3 , Q 4 , Q 5 and Q 6 have the definitions given in the description,
W is halogen, 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, and R 2 is halogen or —O-pivaloyl.

First claim

The invention claimed is:

1. Process for preparing compound of formula (II)

in which
Q is a structural element

where the symbol # indicates the bond to the rest of the molecule and
Q 1 is N or CR 6 ,
Q 2 is N or CR 6 ,
Q 3 is N or C,
Q 4 is O, S, N or NR 7 ,
Q 5 is N or C,
Q 6 is N or CH,
R 6 is hydrogen, (C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, (C 1 -C 4 )cyanoalkyl, (C 1 -C 4 )hydroxyalkyl, (C 1 -C 4 )alkoxy-(C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkoxy-(C 1 -C 4 )alkyl, (C 2 -C 4 )alkenyl, (C 2 -C 4 )alkenyloxy-(C 1 -C 4 )alkyl, (C 2 -C 4 )haloalkenyloxy-(C 1 -C 4 )alkyl, (C 2 -C 4 )haloalkenyl, (C 2 -C 4 )cyanoalkenyl, (C 2 -C 4 )alkynyl, (C 2 -C 4 )alkynyloxy-(C 1 -C 4 )alkyl, (C 2 -C 4 )haloalkynyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 3 -C 6 )cycloalkyl, (C 1 -C 4 )alkyl-(C 3 -C 6 )cycloalkyl, halo(C 3 -C 6 )cycloalkyl, (C 1 -C 4 )alkylthio-(C 1 -C 4 )alkyl, (C 1 -C 4 )alkylsulphinyl-(C 1 -C 4 )alkyl, (C 1 -C 4 )alkylsulphonyl-(C 1 -C 4 )alkyl or (C 1 -C 4 )alkylcarbonyl-(C 1 -C 4 )alkyl,
R 7 is (C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, (C 1 -C 4 )cyanoalkyl, (C 1 -C 4 )hydroxyalkyl, (C 1 -C 4 )alkoxy-(C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkoxy-(C 1 -C 4 )alkyl, (C 2 -C 4 )alkenyl, (C 2 -C 4 )alkenyloxy-(C 1 -C 4 )alkyl, (C 2 -C 4 )haloalkenyloxy-(C 1 -C 4 )alkyl, (C 2 -C 4 )haloalkenyl, (C 2 -C 4 )cyanoalkenyl, (C 2 -C 4 )alkynyl, (C 2 -C 4 )alkynyloxy-(C 1 -C 4 )alkyl, (C 2 -C 4 )haloalkynyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 3 -C 6 )cycloalkyl, (C 1 -C 4 )alkyl-(C 3 -C 6 )cycloalkyl, halo(C 3 -C 6 )cycloalkyl, (C 1 -C 4 )alkylthio-(C 1 -C 4 )alkyl, (C 1 -C 4 )alkylsulphinyl-(C 1 -C 4 )alkyl, (C 1 -C 4 )alkylsulphonyl-(C 1 -C 4 )alkyl or (C 1 -C 4 )alkylcarbonyl-(C 1 -C 4 )alkyl, and
A is hydrogen, cyano, halogen, (C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, (C 2 -C 4 )alkenyl, (C 2 -C 4 )haloalkenyl, (C 2 -C 4 )alkynyl, (C 2 -C 4 )haloalkynyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 3 -C 6 )cycloalkyl, (C 1 -C 4 )alkyl-(C 3 -C 6 )cycloalkyl, (C 1 -C 4 )alkoxy, (C 1 -C 4 )haloalkoxy, (C 1 -C 4 )alkoxyimino, (C 1 -C 4 )alkylthio, (C 1 -C 4 )haloalkylthio, (C 1 -C 4 )alkylsulphinyl, (C 1 -C 4 )haloalkylsulphinyl, (C 1 -C 4 )alkylsulphonyl, (C 1 -C 4 )haloalkylsulphonyl, (C 1 -C 4 )alkylsulphonyloxy, (C 1 -C 4 )alkylcarbonyl, (C 1 -C 4 )haloalkylcarbonyl, aminocarbonyl, (C 1 -C 4 )alkylaminocarbonyl, di-(C 1 -C 4 )alkylaminocarbonyl, (C 1 -C 4 )alkylsulphonylamino, (C 1 -C 4 )alkylamino, di-(C 1 -C 4 )alkylamino, aminosulphonyl, (C 1 -C 4 )alkylaminosulphonyl or di-(C 1 -C 4 )alkylaminosulphonyl,
or A is —O—CF 2 —O— and, together with Q 1 and the carbon atom to which it is bonded, forms a five-membered ring where Q 1 is carbon,
W is 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, first a), a compound Q-H in which Q is as defined above
is reacted with an organozinc base of the structure (NR 3 R 4 )—Zn—R 2 or (NR 3 R 4 ) 2 —Zn in which
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)

in which Q and R 2 each have the definitions given above,
and said compound of formula (IIIa) or (IIIb) is reacted in b) with a compound of formula (I)

in which X is halogen and W and Y each have the definitions given above, in the presence of a catalyst, to give the compound of formula (II).

2. Process according to claim 1 , wherein
Q is a structural element from the group of Q1 to Q15

R 7 is (C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, (C 1 -C 4 )alkoxy-(C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkoxy-(C 1 -C 4 )alkyl, (C 1 -C 4 )alkylthio-(C 1 -C 4 )alkyl, (C 1 -C 4 )alkylsulphinyl-(C 1 -C 4 )alkyl, (C 1 -C 4 )alkylsulphonyl-(C 1 -C 4 )alkyl or (C 1 -C 4 )alkylcarbonyl-(C 1 -C 4 )alkyl,
A is fluorine, chlorine, bromine, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl (CH 2 CFH 2 , CHFCH 3 ), difluoroethyl (CF 2 CH 3 , CH 2 CHF 2 , CHFCFH 2 ), trifluoroethyl, (CH 2 CF 3 , CHFCHF 2 , CF 2 CFH 2 ), tetrafluoroethyl (CHFCF 3 , CF 2 CHF 2 ), pentafluoroethyl, trifluoromethoxy, difluorochloromethoxy, dichlorofluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl,
W is fluorine, chlorine or bromine,
R 2 is halogen,
X is halogen, and
Y is fluorine, chlorine, bromine, CO 2 R or NO 2 , where R 1 is (C 1 -C 4 )-alkyl.

3. Process according to claim 1 , wherein
Q is a structural element from the group of Q2, Q3, Q10, Q12, Q14 and Q15
R 7 is (C 1 -C 4 )alkyl or (C 1 -C 4 )alkoxy-(C 1 -C 4 )alkyl,
A is trifluoromethyl, fluoroethyl (CH 2 CFH 2 , CHFCH 3 ), difluoroethyl (CF 2 CH 3 , CH 2 CHF 2 , CHFCFH 2 ), trifluoroethyl, (CH 2 CF 3 , CHFCHF 2 , CF 2 CFH 2 ), tetrafluoroethyl (CHFCF 3 , CF 2 CHF 2 ), pentafluoroethyl, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl,
W is fluorine or chlorine,
R 2 is chlorine,
X is bromine or iodine, and
Y is chlorine, bromine, CO 2 R 1 or NO 2 , where R 1 is (C 1 -C 4 )-alkyl.

4. Process according to claim 1 , wherein
Q is the structural element Q3 or Q14
R 7 is methyl, ethyl, n-propyl or isopropyl,
A is trifluoromethyl,
W is fluorine,
R 2 is chlorine,
X is iodine, and
Y is chlorine, bromine, CO 2 R or NO 2 , where R 1 is methyl.

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

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

in which x is the number 1 or 2.

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

8. 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 Q-H.

9. Process according to claim 1 , wherein the compound of formula (I) is used in a total amount of 0.5 to 10.0 equivalents, based on the compound Q-H.

10. Process according to claim 1 , wherein the catalyst is a palladium compound.

11. Process according to claim 1 , wherein the catalyst is tetrakis(triphenylphosphine)palladium(0).

12. 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-pyrrolid

Assignees

• Bayer Cropscience Ag

Inventors

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

Classifications

• C07D491/056

  with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• B01J2531/824

  Palladium · CPC title

• B01J31/2404

  Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring · CPC title

• A01N43/90

  having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system · CPC title