IMPROVED SYNTHESIS OF BETA-CIT AND [C-11] BETA-CIT LABELED AT NITROGEN OR OXYGEN POSITIONS

The important radiotracer precursor 2 beta-carbomethoxy-3 beta-(4-idop henyl)-tropane (beta-CIT, RTI-55) was made in 52% overall yield from c ocaine. Key steps were improved conjugate Grignard addition to anhydro ecgonine methyl ester with >3.5:1 2 beta: 2 alpha-isomer selectivity, and a mild new direct aromatic iodination with I-2 and silver triflate in CH2Cl2. The [C-11]beta-CIT was labeled at either the N or O positi ons with [C-11]methyl triflate; and efficient reversed-phase HPLC was used to preparatively separate [N-C-11]beta-CIT from N-nor-beta-CIT fo r the first time, and a fast solid-phase extraction (SPE) method was a pplied to preparatively separate [O-C-11]beta-CIT from beta-CIT acid p recursor. Copyright (C) 1996 Elsevier Science Inc.