Fluorination mannose triflate

The synthesis of2-deoxy-2- F-fluoro-D-glucose (2-[ F]FDG) [153-155] is another example where the application of microwaves can reduce the synthesis time and increase the radiochemical yields. An initial optimization of the standard nucleophilic fluorination with mannose triflate under microwave conditions cut short... 

Schematic representation of a chemical reaction circuit used in the production of 2-deoxy-2-fluoro-D-glucose (FDG). Five sequential processes are shown (() concentration of dilute fluoride ion with the use of a miniaturized anion exchange column located in a rectangle-shaped fluoride concentration loop, (ii) solvent exchange from water to dry MeCN, (Hi) fluorination of the D-mannose triflate precursor 1, (tv) solvent exchange back to water.

In the first instance, research focused on investigating if the fluorination step could be conducted within microreactors. Steel [47] used a microfluidic chip [channel dimensions, 300 pm (wide) x 50 pm (deep)], where a solution of mannose triflate (44) in anhydrous acetonitrile is reacted with a premade complex from [ F] KF, Kryptofix 2.2.2 and K2CO3 in acetonitrile. They reported a 40% conversion for the radiolabeling reaction [(44) to (45)] when a residence time of 2 min was used. 

Gillies and coworkers [48,49] subsequently used a polycarbonate microreactor, in which a chamber was designed to effect very rapid turbulent mixing. The microreactor was used to conduct the fluorination of mannose triflate (44), followed by acid hydrolysis of the intermediate (45) to synthesize [ F]fluorodeoxyglucose ([ F] FDG) (46) (Scheme 6.15), whereby 50% overall incorporation of the radiolabel was achieved with a residence time of just 4 s. However, the polymeric material did limit what solvents could be used within the system. 

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