Abbott Laboratories Corporation

Matthew John Peterson

Anthony Ralph Haight

Margaret Chi-Ping Hsu

Howard E Morton

Yi-Yin Ku

James J Napier

Steven J Wittenberger

Jien-Heh J Tien

Steven A King

Russell Drew Cink

David A Riley

Daniel J Plata

David R Hill

Marvin Robert Leanna

Bikshandarkoil A Narayanan

Michael Rasmussen

Arthur J Cooper

Eric J Stoner

Maureen Ann McLaughlin

Elaine C Lee

Tim Grieme

Prasad S Raje

Mahendra N Deshpande

Weijang Zhang

An efficient arylation technique for use in the synthesis of erythromycin derivatives, involving a modified Heck reaction which employs less than six mole percent of palladium catalyst and no phosphine is disclosed. With this modified Heck reaction, an O-alkenylaryl macrolide can be obtained in a much shorter reaction time than under conventional Heck reaction conditions. The modified Heck reaction can be utilized in a method for phosphine-free arylation of an O-allylic erythromycin derivative, in a method for preparing an O-alkenylaryl erythromycin A derivative, or in a method for preparing a 2', 4&#x2033;-hydroxyl protected 6-O-alkenylaryl erythromycin A derivative.

Arylation method for the functionalization of O-allyl erythromycin derivatives

In one aspect, the invention relates to a process for preparing 6-O-substituted erythromycin derivatives comprising reacting 2&prime;-substituted and optionally 4&Prime;-substituted 9-oxime erythromycin derivatives with an alkylating agent in the presence of a palladium catalyst and phosphine. In another aspect, the invention relates to processes for preparing 6-O-substituted erythromycin ketolides using the palladium-catalyzed alkylation reaction.

Process for preparing 6-o-substituted erythromycin derivatives

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Gurnee, IL, United States of America

Matthew John Peterson