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

The synthesis of the precursor for [ 11 C]carfentanil and the precursor labelling with 11 C 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 H 2 O 2 /K 2 CO 3 /DMSO reaction method significantly increased the yield of this chemical transformation (up to 84%). A simple and straight‐forward synthesis of [ 11 C]carfentanil was achieved by combining in‐loop methylation of the ammonia salt of the precursor by [ 11 C]CH 3 I, 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 [ 11 C]CH 3 I of [ 11 C]carfentanil was 64±12% ( n =6) with the synthesis time of 21 min. The radiochemical purity was >98%. Comparatively high specific radioactivity of [ 11 C]carfentanil [11.2±4.8 Ci/μmol (EOS, n =5)] was partially attributed to the use of [ 11 C]methane target gas for production of carbon‐11 methyl iodide. Copyright © 2003 John Wiley & Sons, Ltd.