Nouvelles substances antihistaminiques à action prolongée: les 1‐4 bis (aralcoyl) pipérazines

Abstract

Préparation et propriétés d'une série de dérivés nouveaux de la pipérazine de formule généralePropriétés biologiques de ces produits.

New Manufacturing Procedure of Cetirizine

“…The synthesis of N,N′-disubstituted piperazine 5 is described in the literature 12 chloride (10). In our manufacturing process a solution of 4chlorobenzhydryl chloride (10) in toluene was prepared starting from purchased 4-chlorobenzophenone (12). It is important to note that the starting material 12 had to meet very strict purity requirements: no quantity of its characteristic impurities (benzophenone, 2-or 3-chlorobenzophenone, or any dichlorobenzophenone isomer) should exceed 0.1%; otherwise final product 1 will fall short of the required purity.…”

“…We decided to pass through 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethanol ( 5 ) and to apply a simple, chemoselective O-alkylating agent, resulting in an intermediate in high yield, which can easily be transformed to cetirizine dihydrochloride ( 1 ) (Scheme ). The synthesis of N , N ′-disubstituted piperazine 5 is described in the literature by N-alkylation of the commercially available N -(2-hydroxyethyl)piperazine ( 11 ) with 4-chlorobenzhydryl chloride ( 10 ). In our manufacturing process a solution of 4-chlorobenzhydryl chloride ( 10 ) in toluene was prepared starting from purchased 4-chlorobenzophenone ( 12 ).…”

“…The solution of compound 10 in toluene was introduced into the N-alkylation reaction of N -(2-hydroxyethyl)piperazine ( 11 ). According to the literature, compound 5 is an oil with an extremely high boiling point even under reduced pressure (205–208 °C at 0.1 Hgmm), which was later characterized also in the form of its dihydrochloride salt . We succeeded in developing a simple and productive technology, avoiding the purification of intermediate 5 by distillation.…”