Physicochemical characterization of ezetimibe and its impurities

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)].…”

“…By combination of all above-mentioned equations, the extended rate Eq. (6) can be derived from which the relationship DOI 10.1002/jps.24070 (Eq (7). between the k obs and the hydroxide concentration (or pH-if logarithmical scale is used) is apparent:…”

“…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.…”

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

Study on the HPLC‐based separation of some ezetimibe stereoisomers and the underlying stereorecognition process

“…5 In contrast to Ez, research studies focused on the separation of its stereoisomers have been relatively limited, and only few workers have attempted chiral resolution of Ez stereoisomers by HPLC. [6][7][8] For example, Filip et al 6 achieved the separation of (RRS)-Ez from Ez on a Hypersil Gold C18 column by RP-HPLC analysis. Radhakrishnan and Subba Rao 7 used a Chiralpak IC column for the separation of Ez and (RRS)-Ez with mobile phase containing hexane/2proponal/TFA.…”