131278-84-7Relevant articles and documents
The role of diastereomer impurity in oiling-out during the resolution of trans -4-methyl-2-piperidine carboxylic ethyl ester enantiomers by crystallization
Ren, Riju,Sun, Dengqiong,Wei, Tingting,Zhang, Shixin,Gong, Junbo
, p. 709 - 716 (2014)
Isolating enantiomers by crystallization via diastereomer salt formation is widely used in the pharmaceutical industry. Unfortunately, we found that, when some diastereomer impurity exists, oiling-out will take place and significantly decrease the resolution efficiency. To identify the role of impurities in oiling-out, three series of chiral resolution of trans-4-methyl-2-piperidine carboxylic ethyl ester (trans-4MPE) with different levels of diastereomer impurity were performed. Using process analytical technologies (PAT) technologies, the demixing region was identified by measuring TL-L curves and supersolubility curves for different series. It was found that a series with a higher level of impurity has a higher TL-L point and a wider demixing region. Besides, it seems that the resolution efficiency through oiling-out, as well as the crystallization kinetics, was significantly decreased. Here we initially put forward this particular diastereomer purification problem, where the impurity has a positive effect on oiling-out. To reduce or eliminate oiling-out, an efficient prepurification strategy must be ensured.
METHOD FOR THE PREPARATION OF PROCESS INTERMEDIATES FOR THE SYNTHESIS OF ARGATROBAN MONOHYDRATE
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Page/Page column 57-58, (2012/10/18)
Object of the present invention is a method for the synthesis of a key intermediate for the synthesis of Argatroban monohydrate, ethyl (2R,4R)-1-[(2S)-2-amino-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4- methylpiperidine-2-carboxylate compounded with HCl.