Process enrichment, case studies

A bulk lot sample of drug substance contained an unknown process-related impurity at 0.4% in case study B.7. To meet project time lines, it was necessary to identify the impurity. Mass spectral data indicated that the impurity had a molecular weight of M+12 (compared to the parent). LC/MS/ MS data indicated that the change was located in the sugar portion of the molecule. Isolation and NMR analysis was required to provide more structural information on the impurity. This again was a process-related impurity not observed in forced degradation studies therefore, effort was placed on finding an enriched mother liquor sample. 

The modeling procedure described in Subsect. 2.4.2 addresses the work processes during the conceptual design of chemical processes. It covers the knowledge acquisition from stakeholders by means of field studies, the creation of conceptual semi-formal work process models, and their subsequent enrichment and formalization. The methodology has been successfully applied in several case studies conducted in industry (cf. Sect. 5.1). This modeling procedure is supposed to be extended... 

The basic aim of this chapter is to illustrate the way in which the various defects we have introduced in previous chapters can form partnerships that enrich the properties of materials and the processes that transpire within them. The logic of the chapter is to provide evidence for this viewpoint through the medium of case studies. As usual, we have not been exhaustive. 

For decades, fluorine was a laboratory curiosity and it was studied mainly by mineral chemists. As is often the case, it was coincidence and not planned research that gave rise to fluorine chemistry. The development of the organic chemistry of fluorine is a direct consequence of the Manhattan Project in order to build nuclear weapons, the isotopic enrichment of natural uranium into its radioactive isotope was needed. For this purpose, the chosen process involved gas diffusion, which required the conversion of uranium into gas uranium hexafluoride (UFs) was thus selected. In order to produce UFe gas on a large scale, fluorhydric acid and elemental fluorine were needed in industrial quantities. This was the birth of the fluorine industry. 

In a related observation, Furstner and co-workers reported that while both the FMC and the MC2 lead to the same E Z alkene ratio in the case of 18-RCM, the use of the same conditions with 19 leads to product enriched selectively in either of the two isomers <02MI657> depending on catalyst selection (Scheme 9). Furstner notes that this "illustrates the subtle influence of remote substituents on the stereochemical outcome of RCM in the macrocyclic series." Studies concerning the effects of chelation of the reactivity of ruthenium carbene complexes were reported by Furstner and co-workers <02OM331>. Paquette and co-workers observed that the use of either the GMC or the MC2 led to different outcomes in the macrocyclization RCM of 1,2-amino-alcohol-templated ene-dienes <02HCA3033, 02MI615> hinting that catalyst selection is also an important consideration in those processes. 

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