169518-65-4

Upstream product

• 98-54-4 para-tert-butylphenol 
• 108-95-2 phenol 
• 1393123-16-4 [⁽¹⁸⁾F]-2-bromo-4-fluorophenol 
• 2198-66-5 2-bromo-4-tert-butylphenol 
• 269409-70-3 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol 
• 3282-30-2 pivaloyl chloride 
• 1239573-10-4 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl pivalate 
• 480438-75-3 t-butyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl carbonate 
• 71597-85-8 (p-hydroxyphenyl)boronic acid 

Relevant academic research and scientific papers

Synthesis of no-carrier-added 4-[18F]fluorophenol from 4-benzyloxyphenyl-(2-thienyl)iodonium bromide

4-[18F]Fluorophenol is a versatile synthon for the synthesis of more complex radiopharmaceuticals bearing a 4-[18F]fluorophenoxy moiety. In order to prepare 4-[18F]fluorophenol in no-carrier-added (n.c.a.) form only a nucl

Alcohol-Enhanced Cu-Mediated Radiofluorination

The potential of many 18F-labeled (hetero)aromatics for applications in positron emission tomography remains underexplored because convenient procedures for their radiosynthesis are lacking. Consequently, simple methods to prepare radiofluorinated (hetero)arenes are highly sought after. Herein, we report the beneficial effect of primary and secondary alcohols on Cu-mediated 18F-labeling. This observation contradicts the assumption that such alcohols are inappropriate solvents for aromatic fluorination. Therefore, we developed a protocol for rapid radiolabeling of an extraordinarily broad scope of boronic and stannyl substrates under general reaction conditions. Notably, radiofluorinated indoles, phenols, and anilines were synthesized directly from the corresponding unprotected precursors. Furthermore, the novel method enabled the preparation of radiofluorinated tryptophans, [18F]F-DPA, [18F]DAA1106, 6-[18F]FDA, and 6-[18F]FDOPA.

FLUORINATION METHOD

The present invention relates to a process for producing an organic compound comprising an 18F atom. The compounds comprising an 18F can be useful as PET ligands for use in diagnostics and/or scanning. The process of the invention comprises treating an organoboron compound, which organoboron compound comprises a boron atom bonded to an sp2 hybridised carbon atom, with (i) 18F – and (ii) a copper compound. The invention also provides the use of an organoboron compound, which organoboron compound comprises a boron atom bonded to an sp2 hybridised carbon atom, in a process for producing an organic compound comprising an 18F atom, which process comprises treating the organoboron compound with (i) 18F – and (ii) a copper compound. The invention also provides a compound of formula (XXXVII): wherein: each PGA is independently H or an alcohol protecting group; PGB is H or a carboxylic acid protecting group; each PGC is independently an amine protecting group; Z is a group selected from a boronic ester group, a boronic acid group, a borate group, and a trifluoroborate group; and a is an integer from 0 to 4.

Synthesis of [18F]Arenes via the Copper-Mediated [18F]Fluorination of Boronic Acids

A copper-mediated radiofluorination of aryl- and vinylboronic acids with K18F is described. This method exhibits high functional group tolerance and is effective for the radiofluorination of a range of electron-deficient, -neutral, and -rich aryl-, heteroaryl-, and vinylboronic acids. This method has been applied to the synthesis of [18F]FPEB, a PET radiotracer for quantifying metabotropic glutamate 5 receptors.

A general copper-mediated nucleophilic 18F fluorination of arenes

Molecules labeled with fluorine-18 are used as radiotracers for positron emission tomography. An important challenge is the labeling of arenes not amenable to aromatic nucleophilic substitution (SNAr) with [ 18F]F-. In the

Fluorine Radiolabelling Process

The invention relates to a process for producing a process for producing an 18F-labelled compound, the process comprising treating a compound of formula (I) wherein EDG is an electron-donating group selected from —OH, —OR4, —NHR5 and —NR55R5; R1, R2, X1 and X2 are as defined herein; and R3 is selected from H, X3 and X4, wherein X3 is a monodentate cleavable surrogate group, and X4 is a bidentate cleavable surrogate group which is bonded (a) to said X1 or X2 and (b) to the ring carbon atom para to EDG; with [18F]fluoride in the presence of an oxidant, thereby producing, when R3 in the compound of formula (I) is H, an 18F-labelled compound of formula (II), wherein EDG is as defined above and R1, R2, X1 and X2 are as defined herein; or thereby producing, when R3 in the compound of formula (I) is said monodentate cleavable surrogate group X3, a compound of formula (IIa), wherein EDG′ is O, NR5, —NR55R5 or [OR4]+, and wherein R4, R5, R55, R1, R2, X1, X2 and X3 are as defined herein; or thereby producing, when R3 in the compound of formula (I) is said bidentate cleavable surrogate group X4, a compound of formula (IIc) or a compound of formula (IId), wherein EDG′ is O, NR5, —NR55R5 or [OR4]+, and wherein R4, R5, R55, R1, R2, X1, X2 and X4 are as defined herein

Metal-free oxidative fluorination of phenols with [18F]fluoride

The radiochemical synthesis of [18F]4-fluorophenols is based on phenol umpolung under oxidative conditions and direct nucleophilic fluorination with [18F]fluoride (see scheme, TBAF=tetra-n-butylammonium fluoride, TFA=trifluoroacetic acid). Readily available O-unprotected 4-tert-butyl phenols are used as precursors in this one-pot protocol. The reaction is completed in less than 30 minutes at room temperature and can be performed using standard or microfluidic technology. Copyright

FLUORINE RADIOLABELLING PROCESS

The invention relates to a process for producing a process for producing an 18F-labelled compound, the process comprising treating a compound of formula (I): wherein EDG is an electron-donating group selected from -OH, -OR4, -NHR5 and -NR55R5; R1, R2, X1 and X2 are as defined herein; and R3 is selected from H, X3 and X4, wherein X3 is a monodentate cleavable surrogate group, and X4 is a bidentate cleavable surrogate group which is bonded (a) to said X or X and (b) to the ring carbon atom para to EDG; with [18F]fluoride in the presence of an oxidant, thereby producing, when R3 in the compound of formula (I) is H, an 18F-labelled compound of formula (II), wherein EDG is as defined above and R1, R2, X1 and X2 are as defined herein; or thereby producing, when R3 in the compound of formula (I) is said monodentate cleavable surrogate group X4, a compound of formula (Ilc), wherein EDG' is O, NR5, -NR55R5 or [OR4]+, and wherein R4, R5, R55, R1, R2, X1, X2 and X3 are as defined herein; or thereby producing, when R3 in the compound of formula (I) is said bidentate cleavable surrogate group X4, a compound of formula (IIc) or a compound of formula (IId), wherein EDG' is O, NR5, -NR55R5 or [OR4]+, and wherein R4, R5, R55, R1, R2, X1, X2 and X4 are as defined herein.

Radiosynthesis and evaluation of [18F]Selectfluor bis(triflate)

(Figure Presented) Selectfluor, one of the most reactive and commonly used electrophilic fluorinating N-F reagents, has been radiolabeled with 18F. The resulting new [18F]-labeled N-F reagent is safe, nontoxic, and easy to handle. The combined use of [18F]Selectfluor bis(triflate) and AgOTf allows for the preparation of electron-rich 18F-aromatic compounds through a simple "shake and mix" protocol at room temperature (see scheme; SA=specific activtiy).

Synthesis, labelling and first evaluation of [18F]R91150 as a serotonin 5-HT2A receptor antagonist for PET

In psychiatric disorders such as anxiety, depression and schizophrenia, 5-HT2A receptors play an important role. In order to investigate them in vivo there is an increasing interest in selective and high-affinity radioligands for receptor binding studies using positron emission tomography (PET). Since available radioligands have disadvantages, R91150, which is a selective and high-affinity ligand for 5-HT2A receptors, was labelled with fluorine-18. This was accomplished in six steps via 4-[ 18F]fluorophenol and 1-(3-bromopropoxy)-4-[18F] fluorobenzene within 190 min starting from no-carrier-added [ 18F]fluoride. The overall radiochemical yield was 3.8±2% and the specific activity was at least 335 GBq/μmol at the end of the synthesis. First ex vivo studies in mice proved the uptake of [18F]R91150 in the brain. Radiometabolite studies revealed no radiometabolites in the brain, whereas in the plasma at least two could be detected 30 min p.i. Further preclinical studies are encouraged to evaluate the potential of this new 5-HT2A ligand as a radiotracer for PET. Copyright