Process for preparing dibenzofurans via catalytic heteroannulation

Abstract

The present invention is directed to the synthesis of 2-chloro-cis-[5a(S)-9a(S)-(5a,6,7,8,9,9a-hexahydro)]dibenzofuran-4-carboxylic acid by a stereospecific catalytic heteroannulation synthesis free of undesirable 8-chloro-2,6-methano-2H-3,4,5,6-tetrahydro-1-benzoxocin-10-carboxylic.

I claim: 
     
       1. A process for the preparation of substantially pure 2-chloro-cis-(5a,6,7,8,9,9a-hexahydro)dibenzofuran-4-carboxylic acid by: (a) heating methyl 5-chloro-3-iodosalicylate with 1,3-cyclohexadiene in the presence of palladium(II)acetate, tetrabutylammonium chloride and sodium acetate in a polar medium selected from DMF and N,N-dimethylacetamide to obtain 2-chloro-cis-5a,8,9,9a-tetrahydrodibenzofuran-4-methylester;   (b) hydrolyzing 2-chloro-5a,8,9,9a-tetrahydrodibenzofuran-4-methylester with lithium hydroxide monohydrate to obtain 2-chloro-cis-5a,8,9,9a-tetrahydrodibenzofuran-4-carboxylic acid; and   (c) reducing 2-chloro-cis-5a,8,9,9a-tetrahydrodibenzofuran-4-carboxylic acid to obtain 2-chloro-cis-(5a,6,7,8,9,9a-hexahydro)dibenzofuran-4-carboxylic acid with 5% palladium on carbon.