Process for the preparation of biphenylamines

Patent metadata

Field	Value
Publication number	US-12344586-B2
Application number	US-202017628349-A
Country	US
Kind code	B2
Filing date	Jul 16, 2020
Priority date	Jul 19, 2019
Publication date	Jul 1, 2025
Grant date	Jul 1, 2025

Abstract

The invention relates to a method for the preparation of 2-aminobiphenyls, key intermediates in the preparation of compounds of interest in the agrochemical industry. The process comprises reacting an ortho-substituted aniline and a phenylboro derivative in the presence of a base and a palladium catalyst, said palladium catalyst comprising a palladium source and a biphenyl phosphine ligand of formula (III) or a salt thereof.

First claim

The invention claimed is:

1. A process to prepare a compound of formula (IV) or a salt thereof

wherein
q is an integer selected from the group consisting of 0, 1, 2, 3 and 4;
p is an integer selected from the group consisting of 1, 2, 3, 4 and 5;
R 11 is hydrogen or a nitrogen protecting group;
R 12 is hydrogen;
each R 1 , if present, is independently selected from the group consisting of the halogens; and
each R 3 is independently selected from the group consisting of the halogens;

the process comprising reacting an ortho-substituted aniline and a phenylboro derivative in the presence of a base and a palladium catalyst, said palladium catalyst comprising a palladium source and a biphenyl phosphine ligand,
wherein said ortho-substituted aniline is a compound of formula (I), or a salt thereof

wherein
q, R 1 , R 11 and R 12 are as defined above; and
X 1 is a group capable of transmetalation with palladium;

wherein said phenylboro derivative is a compound of formula (II)

wherein
p and R 3 are as defined above;
y is an integer selected from 0 or 1;

wherein,
when y is 1, then z is an integer selected from 1, 2 or 3;
when y is 0, then z is an integer selected from 1, 2, 3 or 4, and the compound of formula (II) forms a borate accompanied by a cation A having a charge a+;
and
each R 2 is independently selected from the group consisting of hydrogen, halogen, —OH, —OR 9 , and C 1 -C 10 -alkyl, wherein R 9 is C 1 -C 10 -alkyl or C 6 -C 12 -aryl; or wherein, z being 1, two R 2 groups together form a bridging group —O—(CH 2 ) r —O—, wherein r is 2 or 3, so that said two R 2 groups, together with the oxygen atoms and the boron atom, form a 5- or 6-membered ring, where the CH 2 groups are optionally substituted by one or two C 1 -C 4 -alkyl groups;

and
wherein the biphenyl phosphine ligand is a compound of formula (III) or a salt thereof

wherein
m is an integer selected from the group consisting of 0, 1, 2 and 3;
n is an integer selected from the group consisting of 0, 1, 2, 3 and 4;
each R 4 is independently selected from the group consisting of C 1 -C 16 -alkyl, C 3 -C 15 -cycloalkyl, and C 6 -C 10 -aryl;
each R 5 is independently selected from the group consisting of hydrogen, —OR 10 , —SR 10 , —N(R 10 )(R 10 ), C 1 -C 16 -alkyl, C 3 -C 10 -cycloalkyl, halogen, cyano, and C 1 -C 6 -haloalkyl, provided that one R 5 is not hydrogen, wherein R 10 is selected from the group consisting of C 1 -C 16 -alkyl, C 3 -C 10 -cycloalkyl, and C 1 -C 6 -haloalkyl;
each R 6 is independently selected from the group consisting of halogen, cyano, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alcoxyl and C 1 -C 6 -haloalcoxyl;
each R 7 is independently selected from the group consisting of halogen, cyano, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alcoxyl and C 1 -C 6 -haloalcoxyl.

2. The process according to claim 1 , wherein q is 0 or 1.

3. The process according to claim 1 , wherein q is not 0.

4. The process according to claim 1 , wherein p is 2, 3 or 4, and R 3 is in each case fluoro or chloro.

5. The process according to claim 1 , wherein p is 2 or 3, R 3 is in all cases chloro, q is 0 or 1, and R 1 , if present, is fluoro.

6. The process according to claim 1 , wherein p is 0 or 1, R 3 , if present, is chloro, fluoro or —OH, q is 0 or 1, and R 1 , if present, is fluoro, chloro or —OH.

7. The process according to claim 1 , wherein X 1 is a halogen or —OSO 2 R 8 , wherein R 8 is C 1 -C 16 -alkyl, C 1 -C 16 -haloalkyl or C 6 -C 16 -aryl.

8. The process according to claim 1 , wherein X 1 is chlorine.

9. The process according to claim 1 , wherein R 11 and R 12 are both hydrogens.

10. The process according to claim 1 , wherein R 4 is a C 5 -C 15 -cycloalkyl.

11. The process according to claim 1 , wherein both R 4 are cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl.

12. The process according to claim 1 , wherein m is 0 or 1.

13. The process according to claim 1 , wherein m is 1, and R 7 is a C 1 -C 6 alkyl.

14. The process according to claim 1 , wherein both R 5 are selected from C 1 -C 6 -alkyl and C 1 -C 6 -alcoxyl.

15. The process according to claim 1 , wherein one R 5 is hydrogen and the other R 5 is selected from the group consisting of C 1 -C 6 -alkyl and C 1 -C 6 -alcoxyl.

16. The process according to claim 1 , wherein n is 0.

17. The process according to claim 1 , wherein n is 1, R 6 is selected from C 1 -C 6 -alkyl and C 1 -C 6 -alcoxyl, m is 1 and R 7 is selected from C 1 -C 6 -alkyl and C 1 -C 6 -alcoxyl.

18. A process to produce a compound of formula (V), or a salt thereof,

wherein
q is an integer selected from the group consisting of 0, 1, 2, 3 and 4;
p is an integer selected from the group consisting of 1, 2, 3, 4 and 5;
R 11 is selected from hydrogen or a nitrogen protecting group;
Q is C 6 -C 15 -aryl or C 3 -C 15 -heteroaryl, optionally substituted with one or more groups selected from the group consisting of halogen, C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl;
each R 1 , if present, is independently selected from the group consisting of the halogens; and
each R 3 is independently selected from the group consisting of the halogens;
the process comprising preparing
a compound of formula (IV) or a salt thereof according to the process of claim 1 ; and

the process further comprising,
reacting said compound of formula (IV), or a salt thereof, with a compound of formula (VI)
Q-C(═O)—Z   formula (VI)

wherein
Q is a defined above; and
—C(═O)—Z is an acyl precursor.

19. The process according to claim 18 , wherein said compound of Formula (V) is boscalid, bixafen, pyraziflumid or fluxapyroxad, or a salt thereof.

Assignees

• Adama Makhteshim Ltd

Inventors

• Zhen Xi
• Tang Pingping
• Ashush Natali
• Kisin-Finfer Einat

Classifications

• C07D231/14 Primary

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms · CPC title

• C07D213/82

  in position 3 · CPC title

• B01J2531/824

  Palladium · CPC title

• C07C209/68

  from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton · CPC title

• C07C211/52

  the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups · CPC title