Synthesis of the racemate and individual enantiomers of [11C]methylphenidate for studying presynaptic dopaminergic neuron with positron emission tomography

Carbon-11 labeled dl-threo-methylphenidate (methyl-2-phenyl-2-(2-piperidyl)acetate, Ritalin), a psychostimulant drug widely used to treat attention deficit hyperactivity disorder, was prepared in two steps: O-methylation of the N-protected dl-threo-ritalinic acid derivative with [11C]methyl iodide followed by deprotection. The same strategy was applied for the preparation of C-11 labeled individual enantiomers of threo-methylphenidate from N-protected d-threo- or l-threo-ritalinic acid. The subsequent C 18 sep-pak and reverse-phase HPLC purification resulted in ca. 40% radiochemical yield with a total synthesis time of 40 minutes and an average specific activity of 1.5 Ci/μmole (at EOB).

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