Amination of aryl alcohol derivatives

Patent metadata

Field	Value
Publication number	US-9567307-B2
Application number	US-201213978384-A
Country	US
Kind code	B2
Filing date	Jan 6, 2012
Priority date	Jan 7, 2011
Publication date	Feb 14, 2017
Grant date	Feb 14, 2017

Abstract

Embodiments of the invention provide methods and materials for chemical cross-coupling reactions that utilize aryl alcohol derivatives as cross-coupling partners. Embodiments of the invention include methods for the amination of aryl sulfamates and carbamates, which are attractive cross-coupling partners, particularly for use in multistep synthesis. Illustrative embodiments include versatile means to use simple derivatives of phenol as precursors to polysubstituted aryl amines, as exemplified by a concise synthesis of the antibacterial drug linezolid.

First claim

The invention claimed is:

1. A method for making a cross-coupled compound comprising: combining together:
an aryl alcohol compound, wherein the aryl alcohol compound comprises an aryl sulfamate compound;
an amine; and
a transition metal catalyst, wherein the transition metal catalyst comprises nickel or palladium;
wherein the aryl alcohol compound, the amine and the transition metal catalyst are combined so as to allow a cross-coupling reaction between the amine, the aryl alcohol compound and the transition metal catalyst that results in the formation of a cross-coupled compound that comprises a C—N bond between a carbon atom present in the aryl alcohol compound and a nitrogen atom present in the amine, in a yield of at least 25% and wherein the transition metal catalyst is regenerated simultaneously with formation of the cross-coupled compound;
so that the cross-coupled compound is made.

2. The method of claim 1 , wherein the cross-coupling reaction results in the formation of the cross-coupled compound in a yield of at least 50%.

3. The method of claim 1 , wherein the aryl alcohol compound comprises an aryl sulfamate compound.

4. The method of claim 1 , wherein the amine comprises a secondary amine.

5. The method of claim 1 , wherein the aryl alcohol compound comprises a heteroatom.

6. The method of claim 1 , wherein the transition metal catalyst comprises nickel.

7. The method of claim 1 , wherein the transition metal catalyst comprises an air stable Ni(II) precatalyst complex prior to its combination with the amine and the aryl alcohol derivative.

8. The method of claim 1 , wherein the method is used in the synthesis of linezolid.

9. A method for performing a cross-coupling reaction comprising: combining together:
an amine;
an aryl alcohol compound, wherein the aryl alcohol compound comprises an aryl sulfamate compound; and
a transition metal catalyst, wherein the transition metal catalyst comprises nickel or palladium;
wherein the amine, the aryl alcohol compound and the transition metal catalyst are combined so as to allow:
oxidative addition of the transition metal catalyst and generation of a first organo-transition metal species;
reaction between the first organo-transition metal species and the amine and generation of a second organo-transition metal species; and
reductive elimination of the second organo-transition metal species, regeneration of the transition metal catalyst and generation of a cross-coupled compound in a yield of at least 25%;
so that a cross-coupling reaction is performed.

10. The method of claim 9 , wherein the reaction produces the cross-coupled compound in a yield of at least 50%.

11. The method of claim 9 , wherein the amine comprises a secondary amine.

12. The method of claim 9 , wherein the cross coupled compound is an intermediate in a process for the synthesis of linezolid.

13. The method of claim 9 , wherein the transition metal catalyst comprises nickel and the organo-transition metal species comprises an organo-nickel species.

14. The method of claim 9 , wherein the aryl alcohol compound comprises a heteroatom.

15. The method of claim 9 , wherein the reaction is performed as a one-pot synthesis.

16. The method of claim 9 , wherein the coupling reaction is not performed in a glovebox.

17. The method of claim 9 , wherein the transition metal catalyst comprises an air stable Ni(II) precatalyst complex immediately prior to its combination with the amine and the aryl alcohol compound.

18. The method of claim 9 , wherein the method results in the formation of linezolid.

19. A cross-coupled compound made by a process comprising combining together:
an amine;
an aryl alcohol compound, wherein the aryl alcohol compound comprises an aryl sulfamate compound; and
a transition metal catalyst, wherein the transition metal catalyst comprises nickel or palladium;
wherein the amine the aryl alcohol compound and the transition metal catalyst are combined so as to allow chemical reaction between the amine, the aryl alcohol compound and the transition metal catalyst, wherein the reaction results in the formation of a cross-coupled compound in a yield of at least 25% and wherein the transition metal catalyst is regenerated simultaneously with formation of the cross-coupled compound;
so that the cross-coupled compound is made.

20. A method for making a cross-coupled compound comprising: combining together:
an aryl alcohol compound with a chemical structure:

wherein R is a functional group;
an amine with a structure:

wherein R′ and R″ are functional groups; and
a transition metal catalyst, wherein the transition metal catalyst comprises nickel or palladium;
wherein the aryl alcohol compound, the amine and the transition metal catalyst are combined so as to allow a cross-coupling reaction between the amine, the aryl alcohol compound and the transition metal catalyst that results in the formation of a cross-coupled compound with a structure:

in a yield of at least 25% and wherein the transition metal catalyst is regenerated simultaneously with formation of the cross-coupled compound;
so that the cross-coupled compound is made.

Assignees

• Garg Neil K
• Ramgren Stephen D
• Silberstein Amanda L
• Quasdorf Kyle W
• Univ California

Inventors

• Garg Neil K
• Ramgren Stephen D
• Silberstein Amanda L
• Quasdorf Kyle W

Classifications

• C07D263/38 Primary

  attached in position 2 · CPC title

• C07D209/08

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

• C07D209/88

  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 carbon atoms of the ring system · CPC title

• C07D295/096

  with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings · CPC title

• C07D295/033

  with the ring nitrogen atoms directly attached to carbocyclic rings · CPC title