Synthesis of Aliphatic [carbonyl‐¹¹C]Esters Using [¹¹C]Carbon Monoxide

Abstract

Aliphatic esters were labelled with a short-lived radionuclide, 11C with t ½ = 20.3 min, at the carbonyl position using [ 11 C]carbon monoxide via rapid (6 min) photoinduced radical-mediated carbonylation reactions. The esters were prepared from primary, secondary, and tertiary alkyl iodides, and various alcohols, including tert-butyl alcohol and phenol. The use of strong bases was necessary to achieve good radiochemical yields in short reaction times. Isolated decay-corrected radiochemical yields were in the range of 40-68 %.

Radicals in organic synthesis. Part 1

“…291 The synthesis of such compounds is taxing, due to the short half-life of 11 C (t 1/2 ¼20.3 min), which means that the syntheses must utilise simple starting materials, be rapid and not involve tedious purification procedures if useful quantities of material are to be isolated; radical carbonylation fulfils all of these criteria and is simply achieved by the photolysis of an alkyl iodide 450 in the desired alcohol 451 with base under an atmosphere of [ 11 C]O (Scheme 140). A strong, soluble base is essential, as it permits the formation of a small quantity of alkoxide that drives the equilibrium in favour of product formation.…”

C-11 Radiochemistry in Cancer Imaging Applications

“…The [ 11 C]CO, alkyl iodide or alkyl/aromatic amine and suitable solvent were trapped in the high-pressure reactor and irradiated by the mercury lamp at the optimized wavelength and photoirradiation intensity to afford the target [ 11 C-carbonyl] amides with 50 -70% radiochemical yields (decay-corrected) and 65 -90% [ 11 C] CO conversion rate in a reaction time of 5 -7 minutes [204]. The same strategy was also used to make [ 11 C-carbonyl] esters, ketones, and carboxylic acids [218][219][220][221][222]. Although there have been no published reports of the synthesis of carbon-11 radiotracers for imaging cancer using this technique, the reported rapid synthesis times and high specific activities suggest that it will be a valuable approach in the future to the Carbon-11 labeling of target structures which are not compatible with Grignard synthesis.…”

Chemistry for Positron Emission Tomography: Recent Advances in 11C‐, 18F‐, 13N‐, and 15O‐Labeling Reactions

“…To expand the substrate chemotype,other transition metals and radicalmediated methods were used to activate alkyl halides containing b-hydrogen atoms.I n2 016, Rahman et al developed aNi-mediated method for the synthesis of 11 C-carbonyllabeled alkyl amides starting from non-activated alkyl iodides (Scheme 7A). [55][56][57] 2.3.3. Alkyl iodides could also be utilized in free-radical-mediated reactions with [ 11 C]CO to generate 11 C-carbonyl-labeled carboxylic acids,e sters,a nd amides in good RCY (44-76 %) with high molar activity (Scheme 7B).…”