First scale-up to production scale of a ring closing metathesis reaction forming a 15-membered macrocycle as a precursor of an active pharmaceutical ingredient

BILN 2061 ZW (4) is a new chemical entity which shows promising results against the Hepatitis C virus. The major issue in the synthetic route represents the scale-up of a ring closing metathesis reaction to form a 15-membered macrocycle. The parameters chosen for the macrocyclization are discussed, and the experience during large scale synthesis, trouble shooting, and possible improvements for future campaigns are described.