A novel synthesis of the enantiomers of an antihistamine drug by piperazine formation from a primary amine

Article abstract of DOI:10.1055/s-1995-4013

An enantioselective synthesis of each enantiomer of the antihistamine drug 2-(2-{4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl}ethoxy)acetic acid dihydrochloride (1) is described, involving the preparation of the benzhydrylpiperazine portion of the molecule from reaction of each enantiomer of 4-chlorobenzhydrylamine with N,N-bis(2-chloroethyl)-4-methylbenzenesulfonamide. A modification of standard toluenesulfonamide deprotection with hydrogen bromide in acetic acid was introduced, substituting 4-hydroxybenzoic acid for phenol.