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 [ 11 C]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).