A Practical Synthesis of Highly Hindered Biphenyl-2-carboxylates via Nucleophilic Aromatic Substitution of <i>tert</i>-Butyl 2-Methoxybenzoates with Aryl Grignard Reagent

Abstract

The fluorenone derivative ( OPC-34165 ) has potent repairing and protecting activities for peripheral and central nervous system degeneration. A synthesis of the biphenyl-2-carboxylic acid derivative, which is the key intermediate of OPC-34165, is described employing the S N Ar reaction of tert -butyl 2-methoxybenzoate with aryl Grignard reagent in refluxing THF−toluene.