Process for fluorinating compounds

Patent metadata

Field	Value
Publication number	US-9988322-B2
Application number	US-201414539613-A
Country	US
Kind code	B2
Filing date	Nov 12, 2014
Priority date	Nov 12, 2013
Publication date	Jun 5, 2018
Grant date	Jun 5, 2018

Abstract

Methods of preparing a fluorinated aryl or heteroaryl substrate by combining a quaternary ammonium cyanide and an aryl or heteroaryl substrate substituted with at least one chloro, bromo, sulfonyl, or nitro group to thereby provide a mixture, and combining the mixture with hexafluorobenzene to thereby provide the fluorinated substrate.

First claim

What is claimed is:

1. A method of preparing a fluorinated heteroaryl substrate, comprising:
(a) combining a quaternary ammonium cyanide and a heteroaryl substrate having Formula IA or IB:

wherein
A is Cl, Br, SO 2 R 3 , or NO 2 ;
B is H, Cl, Br, SO 2 R 3 , or NO 2 ;
C is H, Cl, Br, SO 2 R 3 , or NO 2 ;
R 1 is CO 2 R 3 , wherein R 3 is optionally substituted C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, heterocycloalkyl, heteroaryl, cycloalkyl, or aryl;
R 2 is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, thereby providing a mixture; and

(b) combining hexafluorobenzene and the mixture to thereby provide the fluorinated heteroaryl substrate having Formula IIA or IIB

wherein D is B or F, and G is B or F.

2. The method of claim 1 , wherein the quaternary ammonium cyanide is tetrabutylammonium cyanide.

3. The method of claim 1 , wherein the quaternary ammonium cyanide is tetramethylammonium cyanide.

4. The method of claim 1 , wherein the quaternary ammonium cyanide is chosen from tetrahexylammonium cyanide, tetrapentylammonium cyanide, tetrapropylammonium cyanide, tetraethylammonium cyanide, tributyl(methyl)ammonium cyanide, tributyl(ethyl)ammonium cyanide, benzyltrimethylammonium cyanide, bis(triphenylphosphoranylidene)ammonium cyanide, triethyl(methyl)ammonium cyanide, and trimethyl(ethyl)ammonium cyanide, dimethylpyrrolidinium cyanide, and diethylpyrrolidinium cyanide.

5. The method of claim 1 , wherein the quaternary ammonium cyanide and the heteroaryl substrate are combined in the presence of a solvent.

6. The method of claim 1 , wherein the hexafluorobenzene and the mixture are combined in the presence of a solvent.

7. The method of claim 1 , further comprising adding a solvent to the mixture before combining the mixture with hexafluorobenzene.

8. The method of claim 5 , wherein the solvent is a polar aprotic solvent.

9. The method of claim 5 , wherein the solvent is one or more of dimethylformamide, dimethylacetamide, tetrahydrofuran, sulfolane, or deuterated analogs thereof.

10. The method of claim 5 , wherein the solvent is acetonitrile or a deuterated analog thereof.

11. The method of claim 5 , wherein the solvent is dimethylsulfoxide or a deuterated analog thereof.

12. The method of claim 5 , wherein from 0.5 to 5 equivalents of the solvent is used per equivalent of the heteroaryl substrate.

13. The method of claim 1 , wherein the quaternary ammonium cyanide and the heteroaryl substrate are combined at room temperature.

14. The method of claim 1 , wherein the hexafluorobenzene and the mixture are combined at room temperature.

15. The method of claim 1 , wherein from 0.5 to 10 equivalents of the quaternary ammonium cyanide is used per equivalent of the heteroaryl substrate.

16. The method of claim 1 , wherein from 0.1 to 5 equivalents of hexafluorobenzene is used per equivalent of the heteroaryl substrate.

17. The method of claim 1 , wherein a difluorinated or a para-fluorinated product is present in an amount less than the amount of Formula IIA or IIB.

Assignees

• Dow Agrosciences Llc
• Univ Michigan Regents
• Univ Michigan

Inventors

• Allen Laura
• Sanford Melanie
• Bland Douglas

Classifications

• C07C25/24 Primary

  Halogenated aromatic hydrocarbons with unsaturated side chains · CPC title

• C07C17/20

  of halogen atoms by other halogen atoms · CPC title

• C07D213/803

  Processes of preparation · CPC title

• C07B39/00 Primary

  Halogenation · CPC title

• C07D213/79 Primary

  Acids; Esters · CPC title