848609-05-2Relevant academic research and scientific papers
The curved front row neil intermediate preparation method
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Paragraph 0145; 0146; 0148, (2019/04/02)
The invention relates to a preparation method for a treprostinil intermediate (I). The preparation method comprises the steps that: a compound of a formula (II) and a compound of a formula (III) or acidic salt thereof react in the presence of a condensing agent to obtain a compound of a formula (IV); the compound of the formula (IV) and a compound of a formula (V) react to obtain a compound of a formula (I). According to the preparation method for the treprostinil intermediate, weinreb amide and alkyne negative ions react to directly obtain a ketone compound (I), so that environment pollution caused by heavy metal (a PCC oxidant) is avoided, and the adoption of a butyl lithium low-temperature reaction method is also avoided. The preparation method for the treprostinil intermediate has the advantages that reaction conditions are mild, the yield is high, the purity of products is high, and the industrial application prospect is wide. (Formulae (I), (II), (III), (IV) and (V) are shown in the specification)
Synthesis of treprostinil: Key claisen rearrangement and catalytic pauson-khand reactions in continuous flow
García-Lacuna, Jorge,Domínguez, Gema,Blanco-Urgoiti, Jaime,Pérez-Castells, Javier
, p. 9489 - 9501 (2019/11/14)
A new synthesis of treprostinil is described using a plug flow reactor in two of the key steps. First, a Claisen rearrangement reaction is described in scaled flow at multigram amounts. Yields and selectivity of this step are sharply improved compared to those from previous syntheses. Second, the key Pauson-Khand reaction in flow is described under catalytic conditions with 5 mol% of cobalt carbonyl and only 3 equiv. of CO. Scaling up of this reaction safely ensures a good yield of an advanced intermediate which is transformed into treprostinil in three steps. Other improvements are the introduction of the carboxymethyl chain into the phenol from the beginning to reduce the protection-deprotection steps. The synthesis is completed in 14% global yield after 12 linear steps from (S)-epichlorhydrin.
Method of preparation of an alkyne with an optically active hydroxyl group in the beta or gamma position of a triple bond and intermediates obtained
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Page/Page column 7-8, (2010/11/25)
The present invention relates to a method of preparation of an alkyne with an optically active hydroxyl group in the β or γ position of a triple bond and intermediates obtained. The method of the invention for preparation of an alkyne with an optically active hydroxyl group in the β position of a triple bond is characterized in that it comprises the reaction, in the presence of a Lewis acid: of a compound of formula (IV): in which: R is a linear or branched alkyl group having from 1 to 6 carbon atoms. and of a compound of formula (V): [in-line-formulae]R′—C≡C-M ??(V) [/in-line-formulae]in which: R′ represents a hydrogen atom, a linear or branched alkyl group having from 1 to 8 carbon atoms, preferably a methyl group or a trialkylsilyl group. M represents a metal, preferably a metal of group (Ia) of the periodic table, preferably lithium. Another object of the invention comprises the production of an alkyne with an optically active hydroxyl group in the γ position of a triple bond by isomerization of an alkyne with an optically active hydroxyl group in the β position previously obtained.
