Selective Nosylation of 1-Phenylpropane-1,3-diol and Perchloric Acid Mediated Friedel-Crafts Alkylation: Key Steps for the New and Straightforward Synthesis of Tolterodine

Abstract

We have developed a new and straightforward synthesis of racemic tolterodine [N,N-diisopropyl-3-(2-hydroxy-5-methyl­phenyl)-3-phenylpropanamine]. The synthesis involves selective nosylation on the primary alcohol of 1-phenylpropane-1,3-diol using 4-nitrobenzenesulfonyl chloride, subsequent diisopropylamine substitution, and Friedel-Crafts alkylation using aqueous perchloric acid.

Key words

drugs - diol - selective sulfonation - nucleophilic substitution - Friedel-Crafts alkylation

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9

The flash column chromatography may be avoided by using crystallization. This is for industrial consideration.