Process for fluorinating compounds

Patent metadata

Field	Value
Publication number	US-9493415-B2
Application number	US-201414539696-A
Country	US
Kind code	B2
Filing date	Nov 12, 2014
Priority date	Nov 12, 2013
Publication date	Nov 15, 2016
Grant date	Nov 15, 2016

Abstract

Methods of preparing a fluorinated substrate by combining potassium fluoride, a quaternary ammonium salt, and a substrate substituted with at least one chloro, bromo, sulfonyl, or nitro group to thereby provide the fluorinated substrate are disclosed.

First claim

What is claimed is:

1. A method of preparing a fluorinated product, comprising: combining potassium fluoride, one or more quaternary ammonium salts, and a substrate, to thereby provide the fluorinated product, wherein the substrate has 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 H, CN, or CO 2 R 3 , wherein each R 3 is, independent of any other, optionally substituted C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, heterocycloalkyl, heteroaryl, cycloalkyl, or aryl; and
R 2 is H, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
and wherein the fluorinated product has 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 salt comprises a tetraalkyl ammonium cation having Formula + N(R 20 )(R 21 )(R 22 )(R 23 ), wherein R 20 -R 23 are, independent of one another, substituted or unsubstituted C 1 -C 40 alkyl, substituted or unsubstituted C 2 -C 40 alkenyl, substituted or unsubstituted C 2 -C 40 alkynyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, or substituted or unsubstituted C 3 -C 8 cycloalkenyl.

3. The method of claim 2 , wherein each R 20 -R 23 are, independent of one another, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, pentyl, isopentyl, hexyl, 2-ethylbutyl, or 2-methylpentyl.

4. The method of claim 1 , wherein the quaternary ammonium salt comprises a trialkyl benzyl ammonium cation having Formula III:

wherein each R 10 -R 12 are, independent of one another, substituted or unsubstituted C 1 -C 40 alkyl or substituted or unsubstituted C 3 -C 8 cycloalkyl.

5. The method of claim 4 , wherein R 10 is C 10 -C 40 alkyl and R 11 and R 12 are, independent of one another, substituted or unsubstituted C 1 -C 6 alkyl.

6. The method of claim 1 , wherein the quaternary ammonium salt comprises an anion chosen from Cl − , Br − , and C 1 -C 6 CO 2 − .

7. The method of claim 1 , wherein the quaternary ammonium salt comprises an anion chosen from OH − , I − , CN − , SCN − , OCN − , CNO − , N 3 − , CO 3 2− , HCO 3 − , HS − , NO 2 − , NO 3 − , SO 4 2− , PO 4 3− , PF 6 − , ClO − , ClO 2 − , ClO 3 − , ClO 4 − , CF 3 CO 2 − , CF 3 SO 3 − , BF 4 − , and C 6 H 6 CO 2 − .

8. The method of claim 1 , wherein the potassium fluoride and substrate are combined, followed by the addition of the quaternary ammonium salt.

9. The method of claim 1 , wherein the quaternary ammonium salt and substrate are combined, followed by the addition of potassium fluoride.

10. The method of claim 1 , further comprising the addition of a solvent.

11. The method of claim 10 , wherein the solvent comprises one or more of dimethylformamide, dimethylacetamide, tetrahydrofuran, sulfolane, or deuterated analogs thereof.

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

13. The method of claim 10 , wherein the solvent comprises dimethylsulfoxide or a deuterated analog thereof.

14. The method of claim 1 , further comprising heating the combination of potassium fluoride, the quaternary ammonium salt, and the substrate to from about 75 to about 200° C.

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

16. The method of claim 1 , wherein from about 0.5 to about 10 equivalents of potassium fluoride is used per equivalent of the substrate.

17. The method of claim 1 , wherein the quaternary ammonium salt is tetrabutylammonium chloride.

18. 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.

19. A method of preparing a fluorinated heteroaryl substrate, comprising: mixing potassium fluoride, one or more tetraalkylammonium salts, a solvent, and a 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 H, CN, or CO 2 R 3 , wherein each R 3 is, independent of any other, optionally substituted C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, heterocycloalkyl, heteroaryl, cycloalkyl, or aryl; and
R 2 is H, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

20. The method of claim 19 , wherein the tetraalkyl ammonium salt is tetrabutylammonium chloride.

Assignees

• Dow Agrosciences Llc
• Univ Michigan

Inventors

• Allen Laura
• Sanford Melanie
• Lee Shin Hee
• Bland Douglas
• Cheng Yang
• Roth Gary
• Muhuhi Joseck M

Classifications

• C07D213/803 Primary

  Processes of preparation · CPC title

• C07D213/127 Primary

  Preparation from compounds containing pyridine rings · CPC title