Comparison of large-scale routes to manufacture chiral exo-2-norbornyl thiourea

Organic Process Research and Development

Volumn 14, Issue 1, 2010, Pages 133-141

  Caille, Seb ^a   Boni, Jerome ^c   Cox, Geoffrey B ^d   Faul, Margaret M ^a   Franco, Pilar ^e   Khattabi, Saab ^d   Klingensmith, Liane M ^a   Larrow, Jay F ^a   Lee, James K ^d   Martinelli, Michael J ^a   Miller, Larry M ^b   Moniz, George A ^a   Sakai, Kenichi ^f   Tedrow, Jason S ^a   Hansen, Karl B ^a  

^a Process and Product Development   (United States)

^b AMGEN INC   (United States)

^c Site Eiffel 81 ^*  (France)

^d Chiral Technologies Inc   (United States)

^e Parc d'Innovation   (France)

^f Aichi 455 8502   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 77149147423     PISSN: 10836160     EISSN: 1520586X     Source Type: Journal    
DOI: 10.1021/op9002328     Document Type: Article

References (20)

1. Jacques, J; Collet, A.; Wilen, S. H. Enantiomers, Racemates and Resolutions; Wiley: New York, 1981.
2. Cox, G. Preparative Enantioselective Chromatography: Blackwell: London, 2005.
3. Caille, S.; Cui, S.; Hwang, T-L; Wang, X.; Faul, M. M. J. Org. Chem. 2009, 74, 3833-3842.
4. Henriksson, M. Homan, E.; Johansson, L.; Vallgarda, J.; Williams, M.; Bercot, E.; Fotsch, C. H.; Li, A.; Cai, G.; Hungate, R. W.; Yuan, C.; Tegley, C.; St. Jean, D.; Han, N.; Huang, Q.; Liu, Q.; Bartberger, M. D.; Moniz, G. A.; Frizzle, M. J. Patent WO 2005116002, 2005.
5. Kershaw, E. E.; Morton, N. M.; Dhillon, H.; Ramage, L.; Seckl, J. R.; Flier, J. S. Diabetes 2005, 54, 1023-1031.
6. Rasmussen, C. R.; Villani, F. J.; Weaner, L. E.; Reynolds, B. E.; Hood, A. R.; Hecker, L. R.; Nortey, S. O.; Hanslin, A.; Coastanzo, M. J; Powel, E. T.; Molinari, A. J. Synthesis 1988, 6, 456-459.
7. Bobyleva, A. A.; Petrushchenkova, I. A.; Lukovsoya, E. V.; Pekhk, T. I.; Dubitskaya, N. F.; Belikova, N. A. Zh. Org. Kim. 1989, 25, 1428.
8. Diveley, W. R.; Buntin, G. A.; Lohr, A. D. J. Org. Chem. 1969, 34, 616-624.
9. Kozma, D.; Tomor, K.; Novak, C.; Pokol, G.; Fogassy, E. J. Therm. Anal. 1996, 46, 1613-1623.
10. The 12 h cycling time improved the DR of resultant salt 6 for the resolution and the subsequent recrystallizations. Compound (±)-9 was prepared accordingto a reported procedure: Eddine, A. C.; Daich, A.; Jilale, A.; Decroix, B. Heterocycles 1999, 57, 2907-2915.
11. (a) Becher, J.; Frandsen, E. J. Tetrahedron 1977, 33 (3), 341-343.
12. (b) Zhang, Y.; Wei, T.; Lu, J. Synth. Commun. 1998, 28 (17), 3243-3248.
13. 0 is the dead time of the column.
14. The productivity is defined as the amount of desired enantiomer recovered from the column/amount of chiral stationary phase in the column/time from beginning of first peak to end of second peak. The units are normalized to kg of enantiomer/kg of CSP/24 h.
15. Selectivity is defined as the ratio between the k′ constant of the second peak and the k′ constant of the first peak (k′ second peak/k′ first peak).
16. Nicoud, R. M.; Seidel-Morgenstern, A. Isol. Purif. 1996, 2, 165.
17. i is the concentration of the species in the solid phase.
18. HELP is a proprietary chromatographic modeling software developed by Novasep.
19. Varicol is an advanced, multicolumn chromatographic process developed and patented by Novasep.
20. The total pressure drop generated had an average value of 27 bar.