Stereoinvertive Deoxyamination of trans-2-Aminocyclohexanol Using Bose–Mitsunobu Azidation and Staudinger Reaction for the Stereoselective Synthesis of Edoxaban

Stereoinvertive deoxyamination involving Bose–Mitsunobu azidation and the Staudinger reaction, which proceeds under mild conditions in the presence of a neighboring group, was successfully applied for the synthesis of edoxaban. The one-pot process allowed access to key intermediates of edoxaban without isolating azide intermediates. Furthermore, the efficiency of the Bose–Mitsunobu azidation was dramatically improved by changing the substituent on the neighboring group from the Boc group to a thiazole carbonyl unit.