Practical asymmetric synthesis of RO5114436, a CCR5 receptor antagonist

Organic Process Research and Development

Volumn 14, Issue 3, 2010, Pages 592-599

  Huang, Xiaojun ^a   O'Brien, Erin ^a   Thai, Felicia ^a   Cooper, Gary ^a  

^a ROCHE BIOSCIENCE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 77952898149     PISSN: 10836160     EISSN: 1520586X     Source Type: Journal    
DOI: 10.1021/op100020z     Document Type: Article

References (25)

1. Haycock-Lewandowski, S. J.; Wilder, A.; Åhman, J. Org. Process Res. Dev. 2008, 12, 1094-1103
2. Åhman, J.; Birch, M.; Haycock-Lewandowski, S. J.; Long, J.; Wilder, A. Org. Process Res. Dev. 2008, 12, 1104-1113 and references therein
3. Lee, E. K.; Melville, C. R.; Rotstein, D. M. Chem. Abstr. 2005, 144, 69821
4. PCT Int. Publication Number WO/2005/121145 A2, 2005
5. The list price was $245/100 g for m -fluoroactophenone and $71/100 g for ethyl 3-fluorobenzoate (8) at Fluorochem.
6. See for example
7. Davies, S. G.; Ichihara, O.; Lenior, I.; Walters, I. A. J. Chem. Soc., Perkin Trans. 1 1994, 1411
8. Hsiao, Y.; Rivera, N. R.; Rosner, T.; Krska, S. W.; Njolito, E.; Wang, F.; Sun, Y.; Armstrong, J. D., III; Grabowski, E. J. J.; Tillyer, R. D.; Spindler, F.; Malan, C. J. Am. Chem. Soc. 2004, 126, 9918-9919
9. Hansen, K. B.; Hsiao, Y.; Xu, F.; Rivera, N.; Clausen, A.; Kubryk, M.; Krska, S.; Rosner, T.; Simmons, B.; Balsells, J.; Ikemoto, N.; Sun, Y.; Spindler, F.; Malan, C.; Grabowski, E. J. J.; Armstrong, J. D., III. J. Am. Chem. Soc. 2009, 131, 8798-8804
10. Bunlaksananusorn, T.; Rampf, F. Synlett 2005, 2682-2684
11. Schmid, R.; Foricher, J.; Cereghetti, M.; Schönholzer, P. Helv. Chim. Acta 1991, 74, 370-389. We have multikilograms of catalyst 11 in Roche stock
12. Ozanne, A.; Pouyse'gu, L.; Depernet, D.; François, B.; Quideau, S. Org. Lett. 2003, 5, 2903
13. Parikh, J. P.; Doering, W. E. J. Am. Chem. Soc. 1967, 89, 5505-5507
14. Pennell, A. M. K.; Aggen, J. B.; Wright, J. J. K.; Sen, S.; Chen, W.; Dairaghi, D. J.; Zhang, P. Chem. Abstr. 2005, 143, 306291
15. PCT Int. Publication Number WO/2005/084667 A1, 2005
16. Kuo, S.-C.; Tsai, D. J.-S.; Liao, H. Chem. Abstr. 2006, 145, 124603
17. PCT Int. Publication Number WO/2006/074264 A2, 2006.
18. McCombie, S.; Tagat, J. R.; Vice, S.; Lin, S.-I.; Steensma, R.; Palani, A.; Neustadt, B.; Baroudy, B.; Strizki, J.; Endres, M.; Cox, K.; Dan, N.; Chou, C.-C. Bioorg. Med. Chem. Lett. 2003, 13, 567-571
19. Palani, A.; Shapiro, S.; Clader, J. W.; Greenlee, W. J.; Vice, S.; McCombie, S.; Cox, K.; Strizki, J.; Baroudy, B. M. Bioorg. Med. Chem. Lett. 2003, 13, 709-712
20. Draper, R. W. Chem. Abstr. 2005, 142, 176442
21. PCT Int. Publication Number WO/2005/007608 A2, 2005.
22. Abdel-Magid, A. F.; Carson, K. G.; Harris, B. D.; Maryanoff, C. A.; Shah, R. D. J. Org. Chem. 1996, 61, 3849-3862
23. Several stripping to dryness operations remain that can be optimized for mulitkilogram scale by using solvent exchange operations. This was not completed due to the termination of the work.
24. The scale-up study was not conducted for this final process due to the termination of the program.
25. (R)-Tetrahydrofuran-3-carboxylic acid 3 of 98% ee was purchased from Chirotech Technology Ltd. For preparation, see: Johnson, N. B.; Lennon, I. C.; Moran, P. H.; Ramsden, J. A. Acc. Chem. Res. 2007, 40, 1291-1299