Efficient synthesis of 2,2-disubstituted 4H-Benzo[1,4]oxazin-3-ones or 4H-Benzo[1,4]thiazin-3-ones by nucleophilic aromatic substitution

ORGN 520

Noel A. Powell, Fred L. Ciske, fred.l.ciske@pfizer.com, Cuiman Cai, Daniel D. Holsworth, daniel.holsworth@pfizer.com, Chad Van Huis, and Jeremy J Edmunds, Jeremy.Edmunds@pfizer.com. Michigan Laboratories, Pfizer Global Research & Development, 2800 Plymouth Road, Ann Arbor, MI 48105
An efficient preparation of 2,2-disubstituted 4H-benzo[1,4]oxazine-3-ones and 4H-benzo[1,4]thiazine-3-ones by nucleophilic aromatic substitution is described. For example, nucleophilic substitution of 4-bromo-1-fluoro-2-nitro-benzene with 2-(3,5-difluoro-phenyl)-2-hydroxy-propionic acid ethyl ester followed by nitro reduction and intramolecular cyclization gave 6-bromo-2-(3,5-difluoro-phenyl)-2-methyl-4H-benzo[1,4]oxazin-3-one in high yield.

 

Heterocycles, Aromatics, Metal-Mediated Reactions and Syntheses, Materials, Devices, and Switches
8:00 PM-10:00 PM, Wednesday, 29 March 2006 Georgia World Congress Center -- Ex. Hall B4, Poster

Division of Organic Chemistry

The 231st ACS National Meeting, Atlanta, GA, March 26-30, 2006