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 [ 13 CD 3 ]‐asenapine N ‐oxide proceeded in two synthetic steps. Preparation of [ 13 CD 3 ]‐asenapine 11‐hydroxysulfate and [ 13 C 6 ]‐ N ‐desmethylasenapine paralleled established synthetic protocols with effective utilization of labeled precursors. The synthesis of [ 13 CD 3 ]‐asenapine N + ‐glucuronide was achieved in three chemical steps followed by purification.