Synthesis of 18F‐labelled biphenyls via SUZUKI cross‐coupling with 4‐[18F]fluoroiodobenzene

The SUZUKI reaction of organoboron compounds with 4‐[¹⁸F]fluoroiodobenzene has been developed as a novel radiolabelling technique in ¹⁸F chemistry. The cross‐coupling reaction of p‐tolylboronic acid with 4‐[¹⁸F]fluoroiodobenzene was used to screen different palladium complexes, bases and solvents. Optimized reaction conditions (Pd₂(dba)₃, Cs₂CO₃, acetonitrile, 60°C for 5 min) were further applied to the synthesis of various ¹⁸F‐labelled biphenyls bearing different functional groups. The reaction proceeded in excellent radiochemical yields of up to 94% within 5 min while showing good compatibility to many functional groups. Copyright © 2006 John Wiley & Sons, Ltd.     

Syntheses of meta-[F]Fluorobenzaldehyde and meta-[F]Fluorobenzylbromide from Phenyl(3-Formylphenyl) Iodonium Salt Precursors

¹⁸F‐labeled fluorobenzaldehydes and fluorobenzylbromides are useful synthons for the preparation of positron emission tomography radiopharmaceuticals. Although ortho‐ and para‐[¹⁸F]fluorobenzaldehydes can easily be prepared with high yields, the corresponding meta‐derivatives are more problematic. In order to improve the yield of meta‐[¹⁸F]fluorobenzaldehyde, we used the corresponding diaryliodonium salt precursors, since diaryliodonium salts had already been used as precursors in the preparations of ¹⁸F‐labeled electron‐rich, as well as electron‐deficient, aromatic rings. Diaryliodonium salts with different counter ions [PhIPhCHO]X (X = Cl, Br, OTs, OTf) were synthesized. ¹⁸F radiolabeling was performed using different bases at different temperatures in the presence of a radical scavenger, 2,2,6,6‐tetramethylpiperidine‐N‐oxyl (TEMPO). The best conversion (～80%) to meta‐[¹⁸F]fluorobenzaldehyde was obtained using CsHCO₃ base at a reaction temperature of 110°C. To study iodonium salt counter ion effects on radiofluorination, each precursor was separately treated with Cs[¹⁸F]F/CsHCO₃ in DMF at 110°C for 5 min in the presence of TEMPO. Our observed reactivity order was OTsMeta‐[¹⁸F]fluorobenzaldehyde thus obtained was reduced to the corresponding alcohol with aqueous NaBH₄ at room temperature and then converted to meta‐[¹⁸F]fluorobenzylbromide using triphenylphosphine dibromide. Formation of meta‐[¹⁸F]fluorobenzylbromide was confirmed using high‐performance liquid chromatography and the desired product was purified on a silica Sep ‐ Pak^® plus cartridge. Published in 2011 by John Wiley & Sons, Ltd.     

Baeyer‐Villiger oxidation tuned to chemoselective conversion of non‐activated [18F]fluorobenzaldehydes to [18F]fluorophenols

A reaction pathway via oxidation of [¹⁸F]fluorobenzaldehydes offers a very useful tool for the no‐carrier‐added radiosynthesis of [¹⁸F]fluorophenols, a structural motive of several potential radiopharmaceuticals. A considerably improved chemoselectivity of the Baeyer‐Villiger oxidation (BVO) towards phenols was achieved, employing 2,2,2‐trifluoroethanol as reaction solvent in combination with Oxone or m‐CPBA as oxidation agent. The studies showed the necessity of H₂SO₄ addition, which appears to have a dual effect, acting as catalyst and desiccant. For example, 2‐[¹⁸F]fluorophenol was obtained with a RCY of 97% under optimised conditions of 80°C and 30‐minute reaction time. The changed performance of the BVO, which is in agreement with known reaction mechanisms via Criegee intermediates, provided the best results with regard to radiochemical yield (RCY) and chemoselectivity, i.e. formation of [¹⁸F]fluorophenols rather than [¹⁸F]fluorobenzoic acids. Thus, after a long history of the BVO, the new modification now allows an almost specific formation of phenols, even from electron‐deficient benzaldehydes. Further, the applicability of the tuned, chemoselective BVO to the n.c.a. level and to more complex compounds was demonstrated for the products n.c.a. 4‐[¹⁸F]fluorophenol (RCY 95%; relating to 4‐[¹⁸F]fluorobenzaldehyde) and 4‐[¹⁸F]fluoro‐m‐tyramine (RCY 32%; relating to [¹⁸F]fluoride), respectively.     

C‐Terminal 18F‐fluoroethylamidation exemplified on [Gly‐OH9] oxytocin

The no‐carrier‐added (n.c.a.) ¹⁸F‐fluoroethylamidation of the acid function of the protected nonapeptide Boc–Cys–Tyr(tBu)–Ile–Gln(Mtt)–Asn(Mtt)–Cys–Pro–Leu–Gly–OH forming the labelled peptide hormone derivative [Gly‐(2‐[¹⁸F]fluoroethyl)NH⁹]‐oxytocin is described. The labelling conditions were elaborated using a protected tripeptide, identical to the C‐terminal sequence of oxytocin. The prosthetic group n.c.a. 2‐[¹⁸F]fluoroethylamine was synthesised via cryptate mediated n.c.a. ¹⁸F‐fluorination of N‐Boc‐2‐(p‐toluenesulfonyloxy)ethylamine in DMSO (RCY: ca. 60%) and subsequent deprotection with a radiochemical yield of 46±5%. [¹⁸F]Fluoroethylamine was reacted with Z–Pro–Leu–Gly–OH in presence of the coupling reagent TBTU or with activated esters of the model‐tripeptide. The activated ester method as well as the condensation in presence of TBTU yielded ?90% of the ¹⁸F‐fluoroethyl‐amidated tripeptide. TBTU‐mediated condensation of n.c.a. 2‐[¹⁸F]fluoro‐ethylamine with the C‐terminal free acid group of protected oxytocin gave the radiochemical yield of about 75%. Deprotection under acidic conditions led to the formation of [Gly–(2‐[¹⁸F]fluoroethyl)NH⁹]oxytocin within 75 min with a radiochemical yield of about 30% as measured by analytical HPLC. Copyright © 2002 John Wiley & Sons, Ltd.     

Fully automated synthesis and purification of 4‐(2′‐methoxyphenyl)‐1‐[2′‐(N‐2″‐pyridinyl)‐p‐[18F]fluorobenzamido]ethylpiperazine

We have developed an efficient synthesis method for the rapid and high‐yield automated synthesis of 4‐(2′‐methoxyphenyl)‐1‐[2′‐(N‐2″‐pyridinyl)‐p‐[¹⁸F]fluorobenzamido]ethylpiperazine (p‐[¹⁸F]MPPF). No‐carrier‐added [¹⁸F]F^? was trapped on a small QMA cartridge and eluted with 70% MeCN(aq) (0.4 mL) containing Kryptofix 222 (2.3 mg) and K₂CO₃ (0.7 mg). The nucleophilic [¹⁸F]fluorination was performed with 3 mg of the nitro‐precursor in DMSO (0.4 mL) at 190 °C for 20 min, followed by the preparative HPLC purification (column: COSMOSIL Cholester, Nacalai Tesque, Kyoto, Japan; mobile phase: MeCN/25 mm AcONH₄/AcOH = 200/300/0.15; flow rate: 6.0 mL/min) to afford p‐[¹⁸F]MPPF (retention time = 9.5 min). p‐[¹⁸F]MPPF was obtained automatically with a radiochemical yield of 38.6 ± 5.0% (decay corrected, n = 5), a specific activity of 214.3 ± 21.1 GBq/µmol, and a radiochemical purity of >99% within a total synthesis time of about 55 min. Copyright © 2012 John Wiley & Sons, Ltd.     

(−)‐[18F]Flubatine: evaluation in rhesus monkeys and a report of the first fully automated radiosynthesis validated for clinical use

(?)‐[¹⁸F]Flubatine was selected for clinical imaging of α₄β₂ nicotinic acetylcholine receptors because of its high affinity and appropriate kinetic profile. A fully automated synthesis of (?)‐[¹⁸F]flubatine as a sterile isotonic solution suitable for clinical use is reported, as well as the first evaluation in nonhuman primates (rhesus macaques). (?)‐[¹⁸F]Flubatine was prepared by fluorination of the Boc‐protected trimethylammonium iodide precursor with [¹⁸F]fluoride in an automated synthesis module. Subsequent deprotection of the Boc group with 1‐M HCl yielded (?)‐[¹⁸F]flubatine, which was purified by semi‐preparative HPLC. (?)‐[¹⁸F]Flubatine was prepared in 25% radiochemical yield (formulated for clinical use at end of synthesis, n = 3), >95% radiochemical purity, and specific activity = 4647 Ci/mmol (171.9 GBq/µmol). Doses met all quality control criteria confirming their suitability for clinical use. Evaluation of (?)‐[¹⁸F]flubatine in rhesus macaques was performed with a Concorde MicroPET P4 scanner (Concorde MicroSystems, Knoxville, TN). The brain was imaged for 90 min, and data were reconstructed using the 3‐D maximum a posteriori algorithm. Image analysis revealed higher uptake and slower washout in the thalamus than those in other areas of the brain and peak uptake at 45 min. Injection of 2.5 µg/kg of nifene at 60 min initiated a slow washout of [¹⁸F]flubatine, with about 25% clearance from the thalamus by the end of imaging at 90 min. Copyright © 2013 John Wiley & Sons, Ltd.     

[18F]Fluoride recovery via gaseous [18F]HF

Acidification of target water with H₂SO₄ in a specially constructed glassy carbon/polyethylene apparatus allowed for recovery of up to 82% of [¹⁸F]fluoride as [¹⁸F]HF gas. The [¹⁸F]HF distillate was found to be acid‐free but moist; when passed through a solution of ^tBuPh₂SiOTf, it yielded [¹⁸F]^tBuPh₂SiF. The multivariate design of experiment showed that the key to high yield of [¹⁸F]HF was the efficient degassing of the reaction mixture.     

Synthesis,radiofluorination and first evaluation of (±)‐[18F]MDL 100907 as serotonin 5‐HT2A receptor antagonist for PET

In some psychiatric disorders 5‐HT_2A receptors play an important role. In order to investigate those in vivo there is an increasing interest in obtaining a metabolically stable, subtype selective and high affinity radioligand for receptor binding studies using positron emission tomography (PET). Combining the excellent in vivo properties of [¹¹C]MDL 100907 for PET imaging of 5‐HT_2A receptors and the more suitable half‐life of fluorine‐18, MDL 100907 was radiofluorinated in four steps using 1‐(2‐bromoethyl)‐4‐[¹⁸F]fluorobenzene as a secondary labelling precursor. The complex reaction required an overall reaction time of 140 min and (±)‐[¹⁸F]MDL 100907 was obtained with a specific activity of at least 30 GBq/µmol (EOS) and an overall radiochemical yield of 1–2%. In order to verify its binding to 5‐HT_2A receptors, in vitro rat brain autoradiography was conducted showing the typical distribution of 5‐HT_2A receptors and a very low non‐specific binding of about 6% in frontal cortex, using ketanserin or spiperone for blocking. Thus, [¹⁸F]MDL 100907 appears to be a promising new 5‐HT_2A PET ligand. Copyright © 2008 John Wiley & Sons, Ltd.     

A facile automated synthesis of N‐succinimidyl 4‐[18F]fluorobenzoate ([18F]SFB) for 18F‐labeled cell‐penetrating peptide as PET tracer

A fully automated synthesis of N‐succinimidyl 4‐[¹⁸F]fluorobenzoate ([¹⁸F]SFB) was carried out by a convenient three‐step, one‐pot procedure on the modified TRACERlab FX_FN synthesizer, including [¹⁸F]fluorination of ethyl 4‐(trimethylammonium triflate)benzoate as the precursor, saponification of the ethyl 4‐[¹⁸F]fluorobenzoate with aqueous tetrapropylammonium hydroxide instead of sodium hydroxide, and conversion of 4‐[¹⁸F]fluorobenzoate salt ([¹⁸F]FBA) to [¹⁸F]SFB treated with N,N,N′,N′‐tetramethyl‐O‐(N‐succinimidyl)uranium tetrafluoroborate (TSTU). The purified [¹⁸F]SFB was used for the labeling of Tat membrane‐penetrating peptide (containing the Arg‐Lys‐Lys‐Arg‐Arg‐Arg‐Arg‐Arg‐Arg‐Arg‐Arg‐Pro‐Leu‐Gly‐Leu‐Ala‐Gly‐Glu‐Glu‐Glu‐Glu‐Glu‐Glu‐Glu sequence, [¹⁸F]CPP) through radiofluorination of lysine amino groups. The uncorrected radiochemical yields of [¹⁸F]SFB were as high as 25–35% (based on [¹⁸F]fluoride) (n=10) with a synthesis time of～40 min. [¹⁸F]CPP was produced in an uncorrected radiochemical yields of 10–20% (n=5) within 30 min (based on [¹⁸F]SFB). The radiochemical purities of [¹⁸F]SFB and [¹⁸F]CPP were greater than 95%. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis of a phenolic precursor and its efficient O‐[18F]fluoroethylation with purified no‐carrier‐added [18F]2‐fluoroethyl brosylate as the labeling agent

[¹⁸F]2‐Fluoroethyl‐p‐toluenesulfonate also called [¹⁸F]2‐fluoroethyl tosylate has been widely used for labeling radioligands for positron emission tomography (PET). [¹⁸F]2‐Fluoroethyl‐4‐bromobenzenesulfonate, also called [¹⁸F]2‐fluoroethyl brosylate ([¹⁸F]F(CH₂)₂OBs), was used as an alternative radiolabeling agent to prepare [¹⁸F]FEOHOMADAM, a fluoroethoxy derivative of HOMADAM, by O‐fluoroethylating the phenolic precursor. Purified by reverse‐phase HPLC, the no‐carrier‐added [¹⁸F]F(CH₂)₂OBs was obtained in an average radiochemical yield (RCY) of 35%. The reaction of the purified and dried [¹⁸F]F(CH₂)₂OBs with the phenolic precursor was performed by heating in DMF and successfully produced [¹⁸F]FEOHOMADAM, after HPLC purification, in RCY of 21%. Copyright © 2013 John Wiley & Sons, Ltd.     

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‐HT_2A 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‐HT_2A 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‐HT_2A ligand as a radiotracer for PET. Copyright © 2008 John Wiley & Sons, Ltd.     

Fast [18F]FDG synthesis by alkaline hydrolysis on a low polarity solid phase support

The synthesis of 2‐deoxy‐2‐[¹⁸F]fluoro‐D ‐glucose ([¹⁸F]FDG) has been simplified by the use of a ^tC18 Sep Pak cartridge to effect purification and hydrolysis of the tetraacetylated [¹⁸F]fluoro‐glucose compound ([¹⁸F]TAG). After radiolabelling, this derivative was trapped on a solid phase extraction (SPE) cartridge and the residual reaction solvent (CH₃CN), reagents (K222, K₂CO₃,…) and by‐products removed by washing the support with water. After this cleaning step, the acetyl groups were cleaved on the same ^tC₁₈ column using 2N sodium hydroxide. This fast reaction proceeded near quantitatively (>98%) at room temperature in less than 2 min. The [¹⁸F]FDG was then recovered with a small amount of water, neutralized with a slight excess of 2N hydrochloric acid, buffered for pH with a citrate solution and finally purified on a neutral alumina oxide and a second ^tC18 column. After filtration, the radiochemical yield of this [¹⁸F]FDG isotonic solution after more than 100 production runs was found to be very reliable and reproducible (70±6% decay corrected). The synthesis time was about 22 min. Quality controls showed that the radiochemical purity was higher than 98% and in any case no [¹⁸F]FDM was detected. Only traces of 2‐chloro‐2‐deoxy‐glucose (ClDG) were found in the final sample (64±9 μg/ batch of 16 ml). [¹⁸F]FDG specific activity averaged between 1 and 20 Ci/µmol (EOS). No evaporation and use of ion retardation resin (AG11A8) are required. Moreover, this new approach is suitable for complete remote operation using available single use medical components. Copyright © 2002 John Wiley & Sons, Ltd.     

Automated synthesis of 18F‐labelled analogs of metomidate,vorozole and harmine using commercial platform

Three ¹⁸F‐labelled PET tracers, 2‐[¹⁸F]fluoroethyl 1‐[(1R)‐1‐phenylethyl]‐1H‐imidazole‐5‐carboxylate ([¹⁸F]FETO), 6‐[(S)‐(4‐chlorophenyl)‐(1H)‐1,2,4‐triazol‐1‐yl)methyl]‐1‐(2‐[¹⁸F]fluoroethyl)‐1H‐benzotriazole ([¹⁸F]FVOZ) and 7‐[2‐(2‐[¹⁸F]fluoroethoxy)ethoxy]‐1‐9H‐ β ‐carboline ([¹⁸F]FHAR) were synthesized by a one‐step nucleophilic fluorination using the automated commercial platform TRACERLab FX_FN. The labelled products were obtained with 16–20% isolated decay corrected radiochemical yields after 70–75 min synthesis time. The radiochemical and chemical purities were more than 98% in all cases. The synthesis using commercial platform may make these tracers more accessible for clinical research. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis and stability of S‐(2‐[18F]fluoroethyl)‐L‐homocysteine for potential tumour imaging

The F‐18 labelled methionine derivative S‐(2‐[¹⁸F]fluoroethyl)‐L‐homocysteine ([¹⁸F]FEHCys) was prepared by a one‐pot two‐step synthesis via the protected S‐(2‐bromoethyl)‐L‐homocysteine 1 and S‐(2‐chloroethyl)‐L‐homocysteine 2 precursors. The bromoethyl derivative 1 gave higher radiochemical yields (40% at 5 min) at 100°C compared with the chloro‐analogue (22% at 100°C in 30 min). However, [¹⁸F]FEHCys was found to be unstable in aqueous systems being transformed to the corresponding hydroxyl derivative within 20 min. Copyright © 2008 John Wiley & Sons, Ltd.     

Comparison of pathways to the versatile synthon of no‐carrier‐added 1‐bromo‐4‐[18F]fluorobenzene

The availability of no‐carrier‐added (n.c.a.) 1‐bromo‐4‐[¹⁸F]fluorobenzene with high radiochemical yields is important for ¹⁸F‐arylation reactions using metallo‐organic 4‐[¹⁸F]fluorophenyl compounds (e.g. of lithium or magnesium) or Pd‐catalyzed coupling. In this study, different methods for the preparation of 1‐bromo‐4‐[¹⁸F]fluorobenzene by nucleophilic aromatic substitution reactions using n.c.a. [¹⁸F]fluoride were examined. Of six pathways compared, symmetrical bis‐(4‐bromphenyl)iodonium bromide proved most useful to achieve the title compound in a direct, one‐step nucleophilic substitution with a radiochemical yield (RCY) of 65% within 10 min. Copyright © 2004 John Wiley & Sons, Ltd.     

N‐Arylation of indoles with 4‐[18F]fluoroiodobenzene: synthesis of 18F‐labelled σ2 receptor ligands for positron emission tomography (PET)

The palladium‐mediated N‐arylation of indoles with 4‐[¹⁸F]fluoroiodobenzene as a novel radiolabelling method has been developed. Optimized reaction conditions were elaborated by variation of different catalyst systems (CuI/1,2‐diamines and Pd₂(dba)₃/phosphine ligands), bases and solvents in the reaction of indole with 4‐[¹⁸F]fluoroiodobenzene. Optimized reaction conditions (Pd₂(dba)₃/(2‐(dicyclohexyl‐phosphino)‐2′‐(N,N‐dimethylamino)‐biphenyl, NaOBu^t, toluene, 100°C for 20 min) were applied for the synthesis of ¹⁸F‐labelled σ₂ receptor ligands [¹⁸F]‐11 and [¹⁸F]‐13 which were obtained in 91 and 84% radiochemical yields, respectively. Copyright © 2004 John Wiley & Sons, Ltd.     

Facile synthesis of 2‐deoxy‐2‐[18F]fluorosorbitol using sodium borohydride on aluminum oxide

2‐Deoxy‐2‐[¹⁸F]fluorosorbitol (¹⁸F‐FDS) has become increasingly useful in functional renal imaging. FDS is synthesized by the one‐step reduction of 2‐deoxy‐2‐[¹⁸F]fluoroglucose (¹⁸F‐FDG). To develop a more simple and rapid procedure for ¹⁸F‐FDS synthesis, we examined reduction reactions with solid‐supported NaBH₄. Synthetic yields using BH₄–IRA400 (polymer‐based matrix) and NaBH₄–Al₂O₃ (clay‐based matrix) as solid‐supported reagents were compared. NaBH₄–Al₂O₃ was found to be far superior to BH₄–IRA400 in the FDG reduction reaction. IRA 400 was not suitable for this reaction because it adsorbs FDG, in addition to glucose, with no FDS synthesized when using BH₄–IRA400. By contrast, NaBH₄–Al₂O₃ only required a filtration as workup, affording FDS in 90% yield after a total of 10 min. NaBH₄ on alumina was readily consumed in the reaction within 1 min, regardless of the amount used, by simply stirring with a vortex mixer. Complicated procedures, such as microwave irradiation, were not necessary. This simple operation will allow kit formulation and is suitable for radiosynthesis. In conclusion, clay‐supported reagents showed low absorption and were time saving, which are highly compatible with ¹⁸F‐FDS synthesis.     

No‐carrier added synthesis of 18F‐labelled nucleosides using Stille cross‐coupling reactions with 4‐[18F]fluoroiodobenzene

The radiosyntheses of 5‐(4′‐[¹⁸F]fluorophenyl)‐uridine [¹⁸F]‐11 and 5‐(4′‐[¹⁸F]fluorophenyl)‐2′‐deoxy‐uridine [¹⁸F]‐12 are described. The 5‐(4′‐[¹⁸F]fluoro‐phenyl)‐substituted nucleosides were prepared via a Stille cross‐coupling reaction with 4‐[¹⁸F]fluoroiodobenzene followed by basic hydrolysis using 1 M potassium hy‐droxide. The Stille cross‐coupling reaction was optimized by screening various palladium complexes, additives and solvents. By using optimized labelling conditions (Pd₂(dba)₃/CuI/AsPh₃ in DMF/dioxane (1:1), 20 min at 65°C), 550 MBq of [4‐¹⁸F]fluoroiodobenzene could be converted into 120 MBq (33%, decay‐corrected) of 5‐(4′‐[¹⁸F]fluorophenyl)‐2′‐deoxy‐uridine [¹⁸F]‐12 within 40 min, including HPLC purification. Copyright © 2004 John Wiley & Sons, Ltd.     

Synthesis of 4‐[18F]fluoroiodobenzene and its application in sonogashira cross‐coupling reactions

The first application of a Sonogashira cross‐coupling reaction in ¹⁸F chemistry has been developed. The reaction was exemplified by the cross‐coupling of terminal alkynes (ethynylcyclopentyl carbinol 6 , 17α‐ethynyl‐3,17β‐estradiol 7 and 17α‐ethynyl‐3‐methoxy‐3,17β‐estradiol 8 ) with 4‐[¹⁸F]fluoroiodobenzene. 4,4′‐Diiododiaryliodonium salts were used as precursors for the synthesis of 4‐[¹⁸F]fluoroiodobenzene, enabling the convenient access to 4‐[¹⁸F]fluoroiodobenzene in 13–70% yield using conventional heating or microwave activation. The Sonogashira cross‐coupling of 4‐[¹⁸F]fluoroiodobenzene with terminal alkynes gave the corresponding 4‐[¹⁸F]fluorophenylethynyl‐substituted compounds [¹⁸F]‐9 , [¹⁸F]‐10 and [¹⁸F]‐13 in yields up to 88% within 20 min of starting from 4‐[¹⁸F]fluoroiodobenzene. Copyright © 2003 John Wiley & Sons, Ltd.     

One‐step reductive etherification of 4‐[18F]fluoro‐benzaldehyde with decaborane

Reductive coupling reactions between 4‐[¹⁸F]fluoro‐benzaldehyde ([¹⁸F] 1 ) and different alcohols by use of decaborane (B₁₀H₁₄) as reducing agent have the potential to synthesize 4‐[¹⁸F]fluoro‐benzylethers in one step. [¹⁸F] 1 was synthesized from 4‐trimethylammonium benzaldehyde (triflate salt) via a standard fluorination procedure (K[¹⁸F]F/Kryptofix^® 222) in dimethylformamide at 90°C for 25 min and purified by solid‐phase extraction. Subsequently, reductive etherifications of [¹⁸F] 1 were performed as one‐step reactions with primary and secondary alcohols, mediated by B₁₀H₁₄ in acetonitrile at 60°C. Various 4‐[¹⁸F]fluorobenzyl ethers (6 examples are shown) were obtained within 1–2 h reaction time in decay‐corrected radiochemical yields of 12–45%. Copyright © 2006 John Wiley & Sons, Ltd.