824954-89-4Relevant academic research and scientific papers
Asymmetric synthesis of (S)-mirtazapine: Unexpected racemization through an aromatic ipso-attack mechanism
Van Der Linden, Marco,Borsboom, Judith,Kaspersen, Frans,Kemperman, Gerjan
experimental part, p. 2989 - 2997 (2009/04/07)
An asymmetric synthesis of (S)-mirtazapine has been achieved from the synthesis of the racemate by using (S)-1-methyl-3-phenylpiperazine as the starting material. Unfortunately, significant racemization was encountered in the final step, which involved an electrophilic aromatic ring closure of a alcohol by concentrated sulfuric acid. A significantly higher ee was observed when polyphosphoric acid (PPA) was used instead. A remarkable correlation between the amount of PPA used and the ee of the product was revealed, namely, an increase in the ee upon decreasing the amount of PPA. This trend was paralleled by the formation of an increasing amount of a side-product upon lowering the amount of PPA. The racemization and formation of a side-product can be explained by an ipso-attack mechanism during the electrophilic aromatic ring-closure reaction. This mechanism was supported by a mechanistic study using a deuterium-labeled substrate. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
PROCESS FOR PRODUCING OPTICALLY ACTIVE PIPERAZINE COMPOUND
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Page/Page column 24-25, (2008/12/06)
Provided is a method of producing optically active 1-methyl-3-phenylpiperazine of the formula (11) or salt thereof, comprising the following steps 1 to 4, or steps 5 to 7 and step 4, and a method of producing optically active mirtazapine via this method.
