Phosphonic acid analogs of diclofenac: an Arbuzov reaction of trimethylphosphite with an ortho-quinonoid intermediate

The phosphonic acid analog of the NSAID Diclofenac was efficiently synthesized via an Arbuzov reaction between 2-(2,6-dichloroanilino)benzyl alcohol and trimethyl phosphite followed by TMSBr promoted dealkylation. Seven related phosphonic acids were synthesized using the same novel acid-catalyzed Arbuzov reaction as the key step. (C) 2000 Elsevier Science Ltd. All rights reserved.