Efficient fast screening methodology for optical resolution agents: Solvent effects are used to affect the efficiency of the resolution process

Organic Process Research and Development

Volumn 8, Issue 3, 2004, Pages 532-534

  Borghese, Alfio ^a   Libert, Valery ^c   Zhang, Tony ^b   Alt, Charles A ^b  

^a Eli Lilly Benelux   (Belgium)

^b ELI LILLY AND COMPANY   (United States)

^c NONE

Author keywords

[No Author keywords available]

Indexed keywords

SOLVENT;

ARTICLE; CRYSTALLIZATION; SCREENING; SEPARATION TECHNIQUE; SOLUBILITY;

EID: 3042690465     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op0499627     Document Type: Article

References (29)

1. Letter p is used to designate the diastereomers resulting from reaction of the two constituents having like sign of rotation, and the letter n, to designate the diastereomers formed from constituents of unlike sign (ref 2).
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3. Reinhold, D. F.; Firestone, R. A.; Gaines, W. A.; Chemerda, J. M.; Sletzinger, M. J. J. Org. Chem. 1968, 33, 1209.
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5. 2O (10% v:v) are used. The vials are magnetically stirred or shaken at room temperature for at least 24 h to reach the thermodynamic equilibrium. The vials containing solid are filtered and both the crystal and the mother liquors analyzed for de assessment (HPLC, CZ, GC, polarimetry, etc...).
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9. Sheldon R. A. Chirotechnology: Industrial Synthesis of Optically Active Compounds; Marcel Dekker: New York, 1993; p 186.
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18. 365 -78.8° (c = 2, MeOH)).
19. The absolute configuration of the crystallized salt (S)-1 (D)-alalinol salt was proven by X-ray analysis. It allows establishing the correspondence between the HPLC elution time and the R and S configurations of both enantiomers.
20. Chiral HPLC analytical conditions: Chiralcel-OJ column, 250 mm x 4.5 mm, eluting with heptane/EtOH, 95/5, + 0.1% TFA, flow rate 1 mL/min, at 25°C, detection at 220 nM.
21. Optically impure diastereomeric salts ascertain that the chiral analysis of the mother liquors provide the eutectic composition.
22. The (S)-2 (S)-CSA salt crystallizes from EtOH as proven by X-ray analysis. It allows establishing the correspondence between the HPLC elution time and the R and S configurations of both enantiomers.
23. Chiral HPLC analytical conditions: Chiralcel-OD column, 250 mm x 4.5 mm, eluting with heptane/ethanol, 90/10, + 0.1% DEA, flow rate 1 mL/ min, at 20°C with detection at 240 nM.
24. Similar eutectic values to those found in i-PrOH have been measured for salts of 2 with (+)-10-camphorsulfonic and L-(+)-tartaric acid in EtOH.
25. Salts (phosphate, HCl) of (S)-2 have been shown to form acetone solvates.
26. Evidence of a crystal form change was given by Raman spectroscopy analysis performed during water addition on (L)-tartrate salt of 2, previously crystallized in acetone.
27. Prausnitz, J. M.; Lichtenhaler, R. N.; de Avezedo, E. G. Molecular Thermodynamics of Fluid-Phase Equilibria; New Jersey: Prentice Hall, Inc., 1986.
28. This is the normal behaviour expected when the solvent does not take part in the eutectic species.
29. Prigogine, I.; Defay, R. Thermodynamique Chimique; Desoer: Liège, Belgium, 1950.