A Novel Synthesis of the Enantiomers of an Antihistamine Drug by Piperazine Formation from a Primary Amine

Authors:
  • COC. J. Opalka
    C. J. Opalka
  • TDT. E. D’ambra
    T. E. D’ambra
  • JFJ. J. Faccone
    J. J. Faccone
  • GBG. Bodson
    G. Bodson
  • ECE. Cossement
    E. Cossement
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Abstract
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.