Method for producing fluorovinyl amide compound

Patent metadata

Field	Value
Publication number	US-12281075-B2
Application number	US-201917299602-A
Country	US
Kind code	B2
Filing date	Dec 5, 2019
Priority date	Dec 5, 2018
Publication date	Apr 22, 2025
Grant date	Apr 22, 2025

Abstract

An object of this disclosure provides a novel method for producing a fluorovinyl amide compound and the like. The object is achieved by a method for producing a compound represented by formula (1):

wherein

Rf is —F or fluoroalkyl,

R a1 is —H or an organic group, and

R a2 is —H or an organic group, or

(i) R a1 and R a2 , (ii) R a1 and Rf, or (iii) Rf and R a2 , may be linked to each other,

R b1 is —H or an organic group, and

R b2 is —H or an organic group, or

R b1 and R b2 may be linked together with their adjacent atoms to form a nitrogen-containing ring optionally having one or more substituents,

the method comprising

step A of reacting a compound represented by formula (2):

wherein

R x is a leaving group,

with a compound represented by formula (3) or a salt thereof:

in the presence of a transition metal catalyst.

First claim

The invention claimed is:

1. A method for producing a compound represented by formula (1):

wherein
Rf is -F or fluoroalkyl,
R a1 is-H or an organic group, and
R a2 is -H or an organic group, or
(i) R a1 and R a2 , (ii) R a1 and Rf, or (iii) Rf and R a2 , may be linked to each other,
R b1 is -H or an organic group, and
R b2 is -H or an organic group, or
R b1 and R b2 may be linked together with their adjacent atoms to form a nitrogen-containing ring optionally substituted with one or more substituents,
the method comprising
step A of reacting a compound represented by formula (2):

wherein
R x is a leaving group, and other symbols are as defined above,
with
a compound represented by formula (3) or a salt thereof:

wherein the symbols in the formula are as defined above,
in the presence of a transition metal catalyst.

2. The production method according to claim 1 , wherein Rf is -F or perfluoroalkyl.

3. The production method according to claim 1 , wherein R a1 is -H, an alkyl group optionally substituted with one or more substituents, or an aromatic ring group optionally substituted with one or more substituents.

4. The production method according to claim 1 , wherein R a2 is -H, an alkyl group optionally substituted with one or more substituents, or an aromatic ring group optionally substituted with one or more substituents.

5. The production method according to claim 1 , wherein either R a1 or R a2 is -H, and the other is -H or an aromatic ring group optionally substituted with one or more substituents.

6. The production method according to claim 1 , wherein R x is a halo group or a sulfonic acid ester group.

7. The production method according to claim 1 ,
wherein
R b1 is -L b -R h ,
wherein
R h is
an aliphatic hydrocarbyl group optionally substituted with one or more substituents, wherein one or more heteroatoms selected from the group consisting of O, S, and Si may be inserted into the aliphatic hydrocarbyl group, or
an aromatic ring group optionally substituted with one or more substituents, and L b is a single bond,-NR r -,-O-, or -S-, and R r is -H or an alkyl group.

8. The production method according to claim 1 ,
wherein
R b2 is -L b -R h ,
wherein
R h is
an aliphatic hydrocarbyl group optionally substituted with one or more substituents, wherein one or more heteroatoms selected from the group consisting of O, S, and Si may be inserted into the aliphatic hydrocarbyl group, or
an aromatic ring group optionally substituted with one or more substituents, and L b is a single bond,-NR r -,-O-, or -S-, and R r is -H or an alkyl group.

9. The production method according to claim 8 , wherein R b1 and R b2 are linked together with their adjacent atoms to form a nitrogen-containing heterocyclic ring optionally substituted with one or more substituents.

10. The production method according to claim 1 , wherein the transition metal catalyst is at least one member selected from the group consisting of palladium catalysts, copper catalysts, nickel catalysts, platinum catalysts, and iron catalysts.

11. The production method according to claim 1 , wherein the transition metal catalyst is at least one member selected from the group consisting of palladium catalysts, copper catalysts, and nickel catalysts.

12. The production method according to claim 1 , wherein the transition metal catalyst is a palladium catalyst.

13. The production method according to claim 1 , wherein the reaction of step A is performed in the presence of a coordination compound.

14. The production method according to claim 13 ,
wherein
the coordination compound is a biphenyl compound represented by formula (4-1):

wherein
A 4a is a benzene ring,
A 4b is a benzene ring,
R 4a1 is a phosphino group substituted with two C 1-20 hydrocarbyl groups,
R 4a2 is an alkyl group or an alkoxy group,
R 4a3 , in each occurrence, is the same or different and represents a substituent,
R 4b , in each occurrence, is the same or different and represents a substituent,
n4a is a number of 0 to 3, and
n4b is a number of 0 to 5.

15. The production method according to claim 13 , wherein
the coordination compound is a biphenyl compound represented by formula (4-1):

wherein
A 4a is a benzene ring,
A 4b is a benzene ring,
R 4a1 is a phosphino group substituted with two substituents selected from the group consisting of cyclohexyl, tert-butyl, and adamantyl groups,
R 4a2 is a methyl group or a methoxy group,
R 4a3 , in each occurrence, is the same or different and represents a substituent,
R 4b , in each occurrence, is the same or different and represents a substituent,
n4a is a number of 0 to 3, and
n4b is a number of 0 to 5.

16. The production method according to claim 1 , wherein the reaction of step A is performed in the presence of a base.

17. The production method according to claim 16 , wherein the base has a pKa of 36 to 3.6.

18. The production method according to claim 16 , wherein the base is at least one member selected from the group consisting of
(1) acetates, carbonates, hydrogen carbonates, phosphates, hydrogen phosphates, alkoxide salts, hydroxide salts, hydride salts, ammonium salts, or amide salts of alkaline or alkaline earth metals,
(2) polymer-supported bases,
(3) alkali metals, and
(4) amines.

Assignees

• Daikin Ind Ltd

Inventors

• Hoshiya Naoyuki
• Matsui Motoshi
• Kishikawa Yosuke

Classifications

• C07D263/22

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to other ring carbon atoms · CPC title

• C07D209/44

  Iso-indoles; Hydrogenated iso-indoles · CPC title

• C07D207/27 Primary

  with substituted hydrocarbon radicals directly attached to the ring nitrogen atom · CPC title

• C07C231/12

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

• B01J23/44

  Palladium · CPC title