Practical asymmetric synthesis of a selective endothelin A receptor (ETA) antagonist.
[structure: see text]. A 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.
Song
Z J
ZJ
Department of Process Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA. zhiguo_song@merck.com
Zhao
M
M
Frey
L
L
Li
J
J
Tan
L
L
Chen
C Y
CY
Tschaen
D M
DM
Tillyer
R
R
Grabowski
E J
EJ
Volante
R
R
Reider
P J
PJ
Kato
Y
Y
Okada
S
S
Nemoto
T
T
Sato
H
H
Akao
A
A
Mase
T
T
D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D001572:Benzofurans / Q000138:chemical synthesis; D065128:Endothelin Receptor Antagonists; D011725:Pyridines / Q000138:chemical synthesis; D044022:Receptor, Endothelin A
D000959:Antihypertensive Agents; D001572:Benzofurans; D065128:Endothelin Receptor Antagonists; D011725:Pyridines; D044022:Receptor, Endothelin A