Electrochemical flash fluorination and radiofluorination

Patent metadata

Field	Value
Publication number	US-11779665-B2
Application number	US-201916963463-A
Country	US
Kind code	B2
Filing date	Feb 4, 2019
Priority date	Feb 2, 2018
Publication date	Oct 10, 2023
Grant date	Oct 10, 2023

Abstract

Provided herein are methods of fluorinating organic compounds. The electrochemical fluorination and radiofluorination of organic molecules using the cation pool technique is described, where the 18F and/or 19F-fluorine ions are added after the process of electrochemical oxidation, i.e., after formation of a carbocationic organic compound (i.e., a compound having a carbon atom with a positive charge).

First claim

What is claimed is:

1. A method of producing an 18 F fluorinated organic compound, the method comprising the steps of:
(i) performing electrochemical oxidation on a plurality of organic compounds, thereby forming a plurality of carbocations; and
(ii) subsequently adding a plurality of fluorinated nucleophiles to the plurality of carbocations, wherein the plurality of fluorinated nucleophiles comprises 18 F-fluorinated nucleophiles and 19 F-fluorinated nucleophiles, and wherein the plurality of carbocations is in molar excess relative to the plurality of fluorinated nucleophiles, thereby forming the 18 F fluorinated organic compound; wherein performing electrochemical oxidation comprises performing electrochemical oxidation in a liquid medium which comprises a mixture comprising:
(a) the plurality of organic compounds and an organic solvent;
(b) the plurality of organic compounds, an organic solvent, and an acid;
(c) the plurality of organic compounds, an organic solvent, and a base;
(d) the plurality of organic compounds, an acid, and a base; or
(e) the plurality of organic compounds, an organic solvent, an acid, and a base; and wherein the plurality of organic compounds, the acid and the base are present in an amount effective to stabilize the plurality of carbocations.

2. The method of claim 1 , wherein the method comprises performing electrochemical oxidation at a reduced temperature, and wherein the reduced temperature is less than 0° C.

3. The method of claim 1 , wherein performing electrochemical oxidation comprises performing electrochemical oxidation in the liquid medium which comprises the mixture comprising the plurality of organic compounds, the organic solvent, and the acid.

4. The method of claim 3 , wherein the molar ratio of the organic solvent to the acid is from about 0.8:1 to about 3:1.

5. The method of claim 1 , wherein:
(i) the organic solvent is trifluoroethanol, hexafluoroisopropanol, or a combination thereof;
(ii) the acid is trifluoromethanesulfonic acid, tetrabutylammonium perchlorate, tetrabutylammonium tetrafluoroborate, trifluoroacetic acid, p-toluenesulfonic acid, or a combination thereof; and
(iii) the base is a conjugate base of trifluoromethanesulfonic acid, a conjugate base of tetrabutylammonium perchlorate, a conjugate base of tetrabutylammonium tetrafluoroborate, trifluoroacetic acid, a conjugate base of p-toluenesulfonic acid, or a combination thereof.

6. The method of claim 5 , wherein: (i) the acid is trifluoromethanesulfonic acid and the base is the conjugate base of trifluoromethanesulfonic acid; (ii) the acid is tetrabutylammonium perchlorate and the base is the conjugate base of tetrabutylammonium perchlorate; (iii) the acid is tetrabutylammonium tetrafluoroborate and the base is the conjugate base of tetrabutylammonium tetrafluoroborate; (iv) the acid is trifluoroacetic acid and the base is the conjugate base of trifluoroacetic acid; or (v) the acid is p-toluenesulfonic acid and the base is the conjugate base of p-toluenesulfonic acid.

7. The method of claim 1 , wherein adding the plurality of fluorinated nucleophiles to the plurality of carbocations comprises adding the plurality of fluorinated nucleophiles to the mixture of (a), (b), (c), (d), or (e).

8. The method of claim 1 , wherein each of the plurality of organic compounds comprises a saturated carbon atom.

9. The method of claim 1 , wherein each of the plurality of carbocations forms part of a substituted or unsubstituted aromatic or heteroaromatic ring when in neutral form or is adjacent to a carbonyl moiety, an amide moiety, an ester moiety, a sulfur atom, or a thioether moiety.

10. The method of claim 1 , wherein the plurality of fluorinated nucleophiles comprises K( 18 F)F—K222, cesium fluoride, potassium fluoride, triethylamine trihydrofluoride, or tetrabutylammonium fluoride.

11. The method of claim 1 , wherein the plurality of fluorinated nucleophiles is a no-carrier added plurality of fluorinated nucleophiles.

Assignees

• Univ California

Inventors

• Sadeghi Saman
• Balandeh Mehrdad

Classifications

• A61K51/04 Primary

  Organic compounds · CPC title

• C07B59/001

  Acyclic or carbocyclic compounds · CPC title

• C25B3/23

  Oxidation (halogenation C25B3/27) · CPC title

• C25B9/23

  comprising ion-exchange membranes in or on which electrode material is embedded · CPC title

• C07B59/00 Primary

  Introduction of isotopes of elements into organic compounds {; Labelled organic compounds per se} · CPC title