Study of the enantiomeric separation of an acetamide intermediate by using supercritical fluid chromatography and several polysaccharide based chiral stationary phases

• Published in: Journal of Chromatography A Vol. 1218; no. 30; pp. 4886 - 4891
• Main Authors: Toribio, L., del Nozal, M.J., Bernal, J.L., Bernal, J., Martín, M.T.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 29.07.2011
• Subjects: Acetamides - chemistry; Acetamides - isolation & purification; Alcohols - chemistry; amylose; Amylose - analogs & derivatives; Amylose - chemistry; cellulose; Cellulose - analogs & derivatives; Cellulose - chemistry; Chiral separation; Chiralcel OD-H; Chiralpak AD; Chromatography, Supercritical Fluid - instrumentation; Chromatography, Supercritical Fluid - methods; enthalpy; isopropyl alcohol; Lux Amylose-2; Lux Cellulose-2; Phenylcarbamates - chemistry; SFC; Stereoisomerism; supercritical fluid chromatography; Temperature; SFC; Chiralpak AD; Chiralcel OD-H; Lux Cellulose-2; Lux Amylose-2; Chiral separation
• ISSN: 0021-9673; 1873-3778
• DOI: 10.1016/j.chroma.2010.12.031

Four chiral stationary phases, based on the phenylcarbamate derivatives of amylose or cellulose: Chiralcel OD-H, Chiralpak AD, Lux Cellulose-2 and Lux Amylose-2, were evaluated for the enantiomeric separation of an acetamide chiral intermediate, the (4S-trans)-4-(ethylamino)-4-(N-acetamide)-5,6-dihydro-(6S)-methyl-4H-thieno-[2,3-b]thiopyran-7,7-dioxide, using SFC. The effect of the different modifiers and temperatures, on the separation, was also studied. The chiral separation could not be achieved using the Chiralpak AD column, nevertheless the other columns provided excellent results with analysis times close to 6 min and resolutions higher than 2. The highest enantioresolutions and retentions were obtained with the Lux Cellulose-2 column and 2-propanol as organic modifier. The isoelution temperatures were estimated from the van’t Hoff plots, and in all the cases they were above the temperature range studied which means that the enantiomeric separation was enthalpy driven.