Potential Antiinflammatory Agents. IV. Stereoselective Synthesis of 6-Chloro-5-(3'- and 4'-hydroxycyclohexyl) indan-1-carboxylic Acids related to Metabolites of 6-Chloro-5-cyclohexylindan-1-carboxylic Acid (TAI-284)

Abstract

In the course of synthetic study of metabolites of a new potent antiinflammatory agent, 6-chloro-5-cyclohexylindan-1-carboxylic acid (TAI-284), 5-(cis-and trans-3'-hydroxy-cyclohexyl) indan-1-carboxylic acids (25 and 26) and 5-(cis- and trans-4'-hydroxycyclohexyl) indan-1-carboxylic acids (17 and 16) were stereoselectively prepared by sodium borohydride reduction (equatorial alcohol formation) and catalytic hydrogenation (axial alcohol formation) of the corresponding 3'-oxo and 4'-oxo compounds (24 and 15), respectively. Chlorination of 25, 26, 17 and 16 with molecular chlorine in acetonitrile gave their 6-chloro derivatives (27, 28, 21 and 20), which were correlated with metabolites of TAI-284. Of these indans, 3'-hydroxy compounds (25-28) were prepared as a pair of racemic diastereoisomers.