198641-56-4Relevant academic research and scientific papers
Synthesis method of argatroban intermediate (2R,4R)-4-methyl piperidine-2-ethyl formate
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Paragraph 0026; 0027; 0028; 0036; 0037; 0038; 0046; 0048, (2017/09/01)
The invention relates to a synthesis method of an argatroban intermediate (2R,4R)-4-methyl piperidine-2-ethyl formate compound. The synthesis method comprises the following steps: (1) under the action of a rhodium catalyst and ferric oxalate, carrying out catalytic hydrogenation on (2R)-4-methyl-1-((S)-1-phenethyl)-1,2,3,6-tetrahydropyridine-2-ethyl formate, so that (2R,4R)-4-methyl-1-((S)-1-phenethyl)-2-pyridine ethyl formate is obtained; and (2) under the action of a palladium catalyst and ferric oxalate, removing benzyl, so that the (2R,4R)-4-methyl piperidine-2-ethyl formate is obtained. The synthesis method provided by the invention has the advantages that the ferric oxalate is introduced into a reaction system, two-step reaction yield is increased, especially the efficiency is the highest when the ferric oxalate and a rhodium-silicon dioxide catalyst are used together, and the cost is effectively reduced, so that the synthesis method is applicable to industrial production.
Diastereoselective synthesis of an argatroban intermediate, ethyl (2R,4R)-4-methylpipecolate, by means of a Mandyphos/rhodium complex-catalyzed hydrogenation
Ferraboschi, Patrizia,Mieri, Maria De,Grisenti, Paride,Lotz, Matthias,Nettekoven, Ulrike
, p. 1626 - 1631 (2012/01/03)
The synthetic antithrombotic argatroban is a dipeptide between the nonproteogenic (2R,4R)-4-methyl-2-piperidine carboxylic acid and l-arginine, in turn bonded to a methyltetrahydroquinoline sulfonyl group. An extensive screening of transition metal-based complexes with different ligands was performed in order to identify the best catalyst for the diastereoselective hydrogenation of a suitable 4,5-dehydropiperidine precursor aimed toward a synthesis of the (2R,4R)-4-methyl piperidine moiety. Copyright
