Preparation and functionalization of 6-hydroxy-2,3,4,5-tetrahydro-1H-benzo[d]azepines and their use in the synthesis of 5-HT2c agonists

ORGN 682

John A. Werner, jwerner@lilly.com1, Steven E. Dunlap1, Michael J. Rupp, and Wulf Dullenkopf2. (1) Chemical Product Research and Development, Eli Lilly and Company, Lilly Corporate Center - Drop 4813, Indianapolis, IN 46285, (2) Project Coordination, CARBOGEN AMCIS AG, Schachenallee 29, Aarau, CH-5001, Switzerland
An efficient synthesis of a 6-hydroxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine analog was developed from 5,8-dihydronaphthol. Selective halogenation of this key intermediate afforded either 6,7- or 6,9-disubstituted tetrahydrobenzazepines, depending on the reaction conditions. The optimization and scaleup of a selective ortho-chlorination process will be discussed, along with application of the resulting intermediate in the synthesis of 5-HT2c agonists.

 

Biologically-Related Molecules and Processes
8:00 AM-12:00 PM, Wednesday, August 22, 2007 BCEC -- 258B, Oral

Division of Organic Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007