Efficient in‐loop synthesis of high specific radioactivity [11C]carfentanil

The synthesis of the precursor for ¹¹C]carfentanil and the precursor labelling with ¹¹C have both been improved. The problem ‘bottleneck’ step in the carfentanil precursor synthesis, due to low chemical yield (14%) of intermediates nitrile into amide conversion, has been solved. Application of a H₂O₂/K₂CO₃/DMSO reaction method significantly increased the yield of this chemical transformation (up to 84%). A simple and straight‐forward synthesis of ¹¹C]carfentanil was achieved by combining in‐loop methylation of the ammonia salt of the precursor by ¹¹C]CH₃I, using tetrabutylammonium hydroxide as a base, with a previously developed product purification procedure using a C2 extraction disc. A decay corrected yield with respect to ¹¹C]CH₃I of ¹¹C]carfentanil was 64±12% (n=6) with the synthesis time of 21 min. The radiochemical purity was >98%. Comparatively high specific radioactivity of ¹¹C]carfentanil 11.2±4.8 Ci/μmol (EOS, n=5)] was partially attributed to the use of ¹¹C]methane target gas for production of carbon‐11 methyl iodide. Copyright © 2003 John Wiley & Sons, Ltd.