63106-93-4Relevant articles and documents
Microbiological transformations 34: Enantioselective hydrolysis of a key-lactone involved in the synthesis of the antidepressant milnacipran
Viazzo, Pascale,Alphand, Veronique,Furstoss, Roland
, p. 4519 - 4522 (1996)
The enantioselective hydrolysis of a key-lactone allowing for the synthesis of the antidepressant milnacipran is described. Several biocatalysts were screened in order to achieve this biotransformation, the best results being obtained using whole-cells cultures of the fungi Beauveria sulfurescens and Cunninghamella blakesleeana.
Direct Synthesis of Cyclopropanes from gem-Dialkyl Groups through Double C-H Activation
Clemenceau, Antonin,Thesmar, Pierre,Gicquel, Maxime,Le Flohic, Alexandre,Baudoin, Olivier
, p. 15355 - 15361 (2020/10/20)
Cyclopropanes are important structural motifs found in numerous bioactive molecules, and a number of methods are available for their synthesis. However, one of the simplest cyclopropanation reactions involving the intramolecular coupling of two C-H bonds on gem-dialkyl groups has remained an elusive transformation. We demonstrate herein that this reaction is accessible using aryl bromide or triflate precursors and the 1,4-Pd shift mechanism. The use of pivalate as the base was found to be crucial to divert the mechanistic pathway toward the cyclopropane instead of the previously obtained benzocyclobutene product. Stoichiometric mechanistic studies allowed the identification of aryl- and alkylpalladium pivalates, which are in equilibrium via a five-membered palladacycle. With pivalate, a second C(sp3)-H activation leading to the four-membered palladacycle intermediate and the cyclopropane product is favored. A catalytic reaction was developed and showed a broad scope for the generation of diverse arylcyclopropanes, including valuable bicyclo[3.1.0] systems. This method was applied to a concise synthesis of lemborexant, a recently approved anti-insomnia drug.
Preparation method of levomilnacipran hydrochloride
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Paragraph 0057-0058, (2018/09/28)
The invention relates to the field of chemical medicines and organic synthesis and in particular relates to a preparation method of levomilnacipran hydrochloride. Aiming at solving the problems of anexisting method for preparing the levomilnacipran hydrochloride that the cost is relatively high or a generation process is relatively dangerous so that large-scale industrial production is limited, the preparation method is characterized by comprising the following steps: [1] enabling phenylacetonitrile and (R)-2-chloromethyl ethylene oxide to react under the action of sodium amide to obtain a compound 1; then carrying out hydrolysis cyclization on the compound 1 to obtain a compound 2; [2] enabling the compound 2 and thionyl chloride to react in alcohol, so as to obtain a compound 3; [3] enabling the compound 3 to be subjected to exchange reaction through introducing nitryl and amino, so as to obtain a compound 6; [4] reducing nitryl in the compound 6 and forming salt in situ to obtain the levomilnacipran hydrochloride. The preparation method provided by the invention is applicable to industrial production of the levomilnacipran hydrochloride.
