Asymmetric Synthesis of Functionalizedtrans-Cyclopropoxy Building Block for Grazoprevir

A practical and asymmetric synthesis of a functionalized trans -cyclopropoxy building block for the preparation of the HCV NS3/4a protease inhibitor grazoprevir is reported. Intramolecular S N 2 displacement–ring closure, followed by a Baeyer–Villiger oxidation, yields the desired trans -cyclopropanol with full control of diastereoselectivity. A terminal alkyne is then effectively installed using LiNH(CH 2 ) 2 NEt 2 . Starting from ( S )-epichlorohydrin, the cyclopropoxy building block is prepared in 51% overall yield with >99.8% optical purity without isolation of any intermediates.