Synthesis of stable isotope‐labeled metabolites of asenapine

The stable isotope‐labeled synthesis of four of the major metabolites of asenapine is described. The synthesis of ¹³CD₃]‐asenapine N‐oxide proceeded in two synthetic steps. Preparation of ¹³CD₃]‐asenapine 11‐hydroxysulfate and ¹³C₆]‐N‐desmethylasenapine paralleled established synthetic protocols with effective utilization of labeled precursors. The synthesis of ¹³CD₃]‐asenapine N⁺‐glucuronide was achieved in three chemical steps followed by purification.