Stereoconservative synthesis of the enantiomerically pure precursors of [11C](+)-McN 5652 and [11C](−)-McN 5652

A stereoconservative synthetic route for the preparation of the precursors of [11C](+)-McN 5652 and [11C](−)-McN 5652, also known as [11C]McN-5652-X and [11C]McN-5652-W, is reported. The key steps involved the transformation of the (+)-trans-4-bromophenyl or (−)-trans-4-bromophenyl analogues of (+)-McN 5652 or (−)-McN 5652 to triisopropylsilyl-protected thioethers and conversion of the thioethers to benzoyl thioesters via a one-pot deprotection and esterification sequence. Subsequent formation of a tartrate salt of the benzoyl thioesters provided stable, convenient precursors for the routine radiosynthesis of [11C](+)-McN 5652 and [11C](−)-McN 5652. The radiosyntheses were accomplished by S-methylation with high specific activity [11C]methyl iodide of the phenylsulfides, which were generated in situ from the tartrate salt of the benzoyl thioesters. HPLC analyses of the final products demonstrated that all of the reactions were stereoconservative, with no detectable isomerization or racemization taking place in any of the reaction sequences. [11C](+)-McN 5652 and [11C](−)-McN 5652 were obtained with end of synthesis (EOS) yields of ∽120 mCi and EOS specific activities of ∽4000 Ci/mmol following radiosynthesis and purification procedures that required approximately 25 min. The chemical and radiochemical purities of the final products were greater than 95%. © 1998 John Wiley & Sons, Ltd.