Structure of the major degradant of ezetimibe

Kinetics and Mechanism of the Base-Catalyzed Rearrangement and Hydrolysis of Ezetimibe

“…Analytically pure compound ( 2 ) was obtained after crystallization from ethyl acetate–toluene (1:1); melting point 242°C–244°C. The structure of ( 2 ) was confirmed by 1 H NMR and 13 C NMR spectra and X‐ray analysis (see Supplementary Information) that were consistent with those published elsewhere . Another portion (0.05 g) of compound ( 2 ) was isolated from the aqueous filtrate after its evaporation, extraction (dry ethanol), and column chromatography [silica gel 60 μm; dichloromethane–ethyl acetate (2:1)].…”

“…As early as 1 week after the publication of this article, Barhate and Mohanraj 6 pointed out in their Letter to the Editor, that the interpretation of spectral data in the original paper 5 was wrong. The correct structure of the alkaline degradant-compound (2)-was published a few months later by Filip et al 7 and Sánta et al 8 (Scheme 1). The formation of the same compound (2) under strong acid conditions was reported earlier and its absolute structure was confirmed by X-ray analysis.…”

“…Analytically pure compound (2) was obtained after crystallization from ethyl acetate-toluene (1:1); melting point 242 • C-244 • C. The structure of (2) was confirmed by 1 H NMR and 13 C NMR spectra and X-ray analysis (see Supplementary Information) that were consistent with those published elsewhere. [7][8][9] Another portion (0.05 g) of compound (2) was isolated from the aqueous filtrate after its evaporation, extraction (dry ethanol), and column chromatography [silica gel 60 :m; dichloromethane-ethyl acetate (2:1)]. Finally, the chromatographic column was washed with methanol to give a small amount (∼0.05 g) of a mixture containing according to MS analysis 5-(4-fluorophenyl)-5-hydroxy-2-[(4-fluorophenylamino)-(4-hydroxyphenyl)methyl]-pentanoic acid (3) and 6-(4-fluorophenyl)-2-(4-hydroxyphenyl)-3,4,5,6tetrahydro-2H-pyran-3-carboxylic acid (4) as the main components.…”

An “Anthropic” Modus Operandi of Structure Elucidation by NMR and MS

“…[3][4][5][6] In practice, the holistic approach is implemented through the following working protocol: Any particular sample submitted for structure elucidation is first evaluated by a chief analyst (either an NMR or MS expert) who has been assigned to "manage" the holistic analysis of the sample. From an AA point of view, it is also essential that the inferences drawn from different spectroscopic techniques should be clashed with each other and harmonized (i.e., any discrepancies resolved) in situ and in as an unbiased fashion as possible before coming to a conclusion.…”

A critical review on the use of modern sophisticated hyphenated tools in the characterization of impurities and degradation products

“…This publication came in for criticism by another group [265], yet the correct structure was not proposed. Subsequently, a correct structure for the same was established by a third group [266] through isolation and 1 H, 13 C, COSY, HSQC, HMBC and 1D-NOESY NMR investigations. For confirmation the isolated product was also compared with synthetically prepared compound and found to comply in all respects.…”