Chromatographic resolution of the enantiomers of a pharmaceutical intermediate from the milligram to the kilogram scale

Melatonin receptor agents: Synthesis, resolution by HPLC on polysaccharides chiral stationary phases, absolute configuration, and pharmacology of the enantiomers of (±)‐N‐[2‐(7‐fluoro‐1,2,3,4‐ tetrahydronaphthalen‐1‐yl)ethyl]acetamide

“…Figure 2 illustrates the comparison of racemate and its two enantiomers, whose purity is greater than 99%. A reversal of the enantiomeric elution order by the changeover of the carbamate type phase (Chiralcel OD-H) towards the benzoate type phase (Chiralcel OJ) can be observed 23,25 (Table 1). On Chiralcel OD the (+) forms are eluted first, whatever the mobile phase (and particularly the polar modifier), while on Chiralcel OJ the (−) forms are eluted first.…”

Enantiomers of C5‐chiral 1‐acetyl‐3,5‐diphenyl‐4,5‐dihydro‐(1H)‐pyrazole derivatives: Analytical and semipreparative HPLC separation, chiroptical properties, absolute configuration, and inhibitory activity against monoamine oxidase

“…The semipreparative resolution of compound 2 was performed by using the solid injection technique described elsewhere. 6 In the semipreparative run of 1, 9, and 10, 4 -10 mg of racemate, dissolved in 500 -1000 ml of ethanol or n-hexane -ethanol 50:50 (v/v), was injected on to a 10-mm i.d. OD CSP at 25jC (see Table 4).…”

“…To overcome the low solubility of 2 in ethanol, 2-propanol, n-hexane, or mixtures of these solvents, a solid injection technique 6 was used to apply the racemate onto the Chiralcel OD column on a semipreparative scale. The powdered sample was mixed with 40-micron silica, and the mixture was dry-packed into a pre-column (30 Â 4.6 mm i.d.).…”

Recent applications of stereoselective chromatography

“…127 The most often used preparative chromatographic enantioseparation is simulated moving bed technology applied for such drugs as tramadol (productivity, with a feed concentration of 20 g/l, at a feed flow- 128 guaifenesin (on Chiralcel OD, productivity, 80.6 g/day/kg chiral stationary phase) 129,130 and others (formoterol, aminoglutethimide) 129,131 or for some pharmaceutical intermediates (ester of quinoline mevalonic acid). 132,133 A similar method, called closed-loop steady state recycling, was also used for that purpose. 134 The authors used Chiralpak AD as the chiral stationary phase and reported productivity of 255 g racemate/kg CSP/day, similar to that obtained by simulated moving bed technique.…”