A new approach to the furan degradation problem involving ozonolysis of the trans-enedione and its use in a cost-effective synthesis of eplerenone.
[reaction: see text] Whereas ozonization of furan 3a affords little or no carboxylic acid 5, ozonization of the corresponding trans-enedione 6 afforded carboxylic acid 5 in 82.4% yield (cryst., overall from furan, 100 g scale; after workup with dimethyl sulfide, followed by mildly basic hydrogen peroxide). This new approach to furan degradation is showcased in a cost-effective synthesis of eplerenone, an important new medicine for cardiovascular indications.
Pearlman
Bruce A
BA
Chemical Research and Development, Pfizer, Incorporated, Kalamazoo, Michigan 49001-0102, USA. bruce.pearlman@spcorp.com
Padilla
Amphlett G
AG
Hach
John T
JT
Havens
Jeffrey L
JL
Pillai
Muniraj D
MD