ol016601s_si_001.pdf (98 kB)
Practical Asymmetric Synthesis of a Selective Endothelin A Receptor (ETA) Antagonist
journal contribution
posted on 2001-09-27, 00:00 authored by Zhiguo J. Song, Matthew Zhao, Lisa Frey, Jing Li, Lushi Tan, Cheng Y. Chen, David M. Tschaen, Richard Tillyer, Edward J. J. Grabowski, Ralph Volante, Paul J. Reider, Yoshiaki Kato, Shigemitsu Okada, Takayuki Nemoto, Hiroki Sato, Atsushi Akao, Toshiaki MaseA practical, chromotography-free asymmetric synthesis was developed for the large scale preparation of an endothelin receptor antagonist 2.
This synthesis includes a new efficient process for the preparation of 6-bromo-2,3-dihydrobenzofuran, a stereoselective conjugate addition of
an aryllithium followed by stereospecific addition of the Grignard reagent of the top aryl bromide, and an aminophosphate-mediated sterospecific
intramolecular enolate alkylation, which led to the formation of the five-membered ring bearing three contiguous asymmetric centers.