合成路线1

A synthesis leading to the pure anti isomer has also been reported. Cycloaddition of dichloroketene, generated in situ from trichloroacetyl chloride and Zn-Cu couple, to allyl benzyl ether (I) produces the dichloro cyclobutanone (II). Subsequent reduction of the dichloro compound (II) with Zn dust in AcOH gives 3-(benzyloxymethyl)cyclobutanone (III). Reaction of cyclobutanone (III) with KCN and (NH4)2CO3 furnishes a mixture of the isomeric hydantoins (IV) and (V), separable by column chromatography. The minor anti isomer (V) is subsequently hydrolyzed under alkaline conditions to provide aminoacid (VI). After protection of (VI) as the N-Boc derivative (VII), treatment with t-butyl trichloroacetimidate gives the tert-butyl ester (VIII). Removal of the O-benzyl group of (VIII) by catalytic hydrogenolysis, followed by treatment of the resultant alcohol (IX) with methanesulfonyl chloride provides mesylate (X). The mesylate group of (X) is then displaced with [18F]-potassium fluoride to afford the [18F]-labeled fluoride (XI). Finally, acidic hydrolysis of the N-Boc amino ester (XI) yields the title radiofluorinated compound.