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Continuous‐Flow Multistep Synthesis of Cinnarizine, Cyclizine, and a Buclizine Derivative from Bulk Alcohols
Author(s) -
Borukhova Svetlana,
Noël Timothy,
Hessel Volker
Publication year - 2016
Publication title -
chemsuschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.412
H-Index - 157
eISSN - 1864-564X
pISSN - 1864-5631
DOI - 10.1002/cssc.201501367
Subject(s) - cinnarizine , derivative (finance) , chemistry , continuous flow , organic chemistry , chromatography , biochemical engineering , financial economics , engineering , economics
Cinnarizine, cyclizine, buclizine, and meclizine belong to a family of antihistamines that resemble each other in terms of a 1‐diphenylmethylpiperazine moiety. We present the development of a four‐step continuous process to generate the final antihistamines from bulk alcohols as the starting compounds. HCl is used to synthesize the intermediate chlorides in a short reaction time and excellent yields. This methodology offers an excellent way to synthesize intermediates to be used in drug synthesis. Inline separation allows the collection of pure products and their immediate consumption in the following steps. Overall isolated yields for cinnarizine, cyclizine, and a buclizine derivative are 82, 94, and 87 %, respectively. The total residence time for the four steps is 90 min with a productivity of 2 mmol h −1 .