ol7b02867_si_001.pdf (2.36 MB)
Asymmetric Synthesis of Functionalized trans-Cyclopropoxy Building Block for Grazoprevir
journal contribution
posted on 2017-10-20, 00:48 authored by Feng Xu, Yong-Li Zhong, Hongming Li, Ji Qi, Richard Desmond, Zhiguo J. Song, Jeonghan Park, Tao Wang, Matthew Truppo, Guy R. Humphrey, Rebecca T. RuckA 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
SN2 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(CH2)2NEt2. Starting from (S)-epichlorohydrin, the
cyclopropoxy building block is prepared in 51% overall yield with
>99.8% optical purity without isolation of any intermediates.
