A new, very short preparation of 3-benzoylcyclohexanone, a key building block in ketoprofen synthesis

Abstract

Non-steroidal antiinflammatory (NSAI) agents are one of the largest class of drugs both due to their high number and their therapeutic interest.' NSAI can be classified according their chemical structure and most of the more studied are a-arylpropionic acid derivatives. Ketoprofen 1 (Profenid) is one of the most prominent modem anti-inflammatory drug and its synthesis has stimulated the interest of several researchers. 3-Benzoylcyclohexanone 2 is a key building block of one of the most practical preparation of 1 (Eq. 1) reported by Sagami Chemical Research Center as a patent. Compound 2 was first prepared from cyclohexenone and a-morpholinobenzyl cyanide with a tedious method while, Bennetau et al. recently described a multistep, alternative route to 2 via 5-trimethylsilyl- 3-cyclohexenone. Based in our previous experience in the chemistry of nitroalkanes and in order to devise a new synthesis of the title compound, we now present a convenient, very short preparation of 2 using the easily available phenylnitromethane 5 as starting material.