Isotopic fluorination and applications thereof

Patent metadata

Field	Value
Publication number	US-10590057-B2
Application number	US-201616060665-A
Country	US
Kind code	B2
Filing date	Dec 14, 2016
Priority date	Dec 14, 2015
Publication date	Mar 17, 2020
Grant date	Mar 17, 2020

Abstract

Methods of C—H bond fluorination using non-heme manganese catalyst are described herein. For example, a method comprises providing a reaction mixture including a non-heme manganese catalyst, a substrate comprising an sp3 C—H bond and a fluorinating agent and converting the sp3 C—H bond to a C—F bond in the presence of the non-heme manganese catalyst or a derivative thereof.

First claim

The invention claimed is:

1. A method of fluorination comprising:
providing a reaction mixture including a non-heme manganese catalyst, a substrate comprising an sp 3 C—H bond and a fluorinating agent; and
converting the sp 3 C—H bond to a sp 3 C—F bond via transfer of fluorine to the substrate from a cis-F—Mn—OH species of the non-heme manganese catalyst, wherein the non-heme manganese catalyst is selected from the group consisting of Mn(mep)F 2 , Mn(mcp)(OTf) 2 , Mn(mcp)(OH)(F), Mn(mcp)(O)(F), Mn(pdp)(OTf) 2 , Mn(pdp)(OH)(F), and Mn(pdp)(O)(F).

2. The method of claim 1 , wherein the fluorinating agent comprises an 18 F source to provide a sp 3 C- 18 F bond.

3. The method of claim 2 , wherein the 18 F source is [ 18 F]F − .

4. The method of claim 3 , wherein the [ 18 F]F − is no carrier added.

5. The method of claim 2 , wherein the sp 3 C—H bond is part of an alkyl moiety or cycloalkyl moiety.

6. The method of claim 5 having a radiochemical conversion greater than 50 percent.

7. The method of claim 1 , wherein the substrate includes one or more aryl or heteroaryl moieties.

8. The method of claim 1 , wherein the substrate includes one or more functionalities selected from the group consisting of ester, ether, ketone, cyanide, imide, aryl halide and alkyl halide.

9. The method of claim 1 , wherein the reaction mixture further comprises an oxidant.

10. The method of claim 9 , wherein the oxidant is soluble in solvent of the reaction mixture.

11. The method of claim 1 , wherein the non-heme manganese catalyst is present in the reaction mixture in an amount of 1-30 mol %.

12. The method of claim 2 having a radiochemical conversion of at least 30 percent.

13. The method of claim 2 having a radiochemical conversion of at least 50 percent.

14. The method of claim 1 , wherein solvent of the reaction mixture is acetone or acetonitrile.

15. The method of claim 1 , wherein the substrate is a bioactive compound.

16. The method of claim 15 , wherein the bioactive compound is selected from the group consisting of celestolide, protected fingolimod, N-TFA-rasagiline, ibuprofen ester, protected dopamine, N-Phth-amantadine and derivatives thereof.

17. The method of claim 1 , wherein the reaction mixture is free of phase transfer catalyst.

18. A method of fluorination comprising:
providing a reaction mixture including a non-heme manganese catalyst, a substrate comprising an sp 3 C—H bond and a fluorinating agent; and
converting the sp 3 C—H bond to a sp 3 C—F bond via transfer of fluorine to the substrate from an equatorial ligand position on the non-heme manganese catalyst, wherein the reaction mixture is free of phase transfer catalyst, and the non-heme manganese catalyst is selected from the group consisting of Mn(mep)F 2 , Mn(mcp)(OTf) 2 , Mn(mcp)(OH)(F), Mn(mcp)(O)(F), Mn(pdp)(OTf) 2 , Mn(pdp)(OH)(F), and Mn(pdp)(O)(F).

19. The method of claim 18 , wherein the fluorinating agent comprises an 18 F source to provide a sp 3 C- 18 F bond.

20. The method of claim 19 , wherein the 18 F source is [ 18 F]F − .

21. The method of claim 20 , wherein the [ 18 F]F − is no carrier added.

22. The method of claim 20 , wherein the sp 3 C—H bond is part of an alkyl moiety or cycloalkyl moiety.

23. The method of claim 22 having a radiochemical conversion greater than 50 percent.

24. The method of claim 18 , wherein the substrate includes one or more aryl or heteroaryl moieties.

25. The method of claim 18 , wherein the substrate includes one or more functionalities selected from the group consisting of ester, ether, ketone, cyanide, imide, aryl halide and alkyl halide.

Assignees

• Univ Princeton

Inventors

• Groves John T
• Chen Xinyi

Classifications

• C07C269/06

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

• C07C17/14

  in the side-chain of aromatic compounds · CPC title

• C07C45/63 Primary

  by introduction of halogen; by substitution of halogen atoms by other halogen atoms · CPC title

• C07F13/005

  Compounds without a metal-carbon linkage · CPC title

• C07C231/12

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