Development of a continuous flow scale-up approach of reflux inhibitor AZD6906

Organic Process Research and Development

Volumn 16, Issue 5, 2012, Pages 925-929

  Gustafsson, Tomas ^a   Sörensen, Henrik ^a   Pontén, Fritiof ^a  

^a ASTRAZENECA R AND D   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

BATCH PROCEDURE; CONTINUOUS FLOWS; FLOW REGIMES; PRODUCT QUALITY; REACTION OPTIMIZATION; REDUCED COST; ROBUST METHODS; SCALE-UP;

TOXIC MATERIALS;

CHEMICAL REACTIONS;

EID: 84862062869     PISSN: 10836160     EISSN: 1520586X     Source Type: Journal    
DOI: 10.1021/op200340c     Document Type: Article

References (20)

1. Christer Alstermark, C.; Amin, K.; Dinn, S. R.; Elebring, T.; Fjellström, O.; Fitzpatrick, K.; Geiss, W. B.; Gottfries, J.; Guzzo, P. R.; Harding, J. P.; Holmén, A.; Kothare, M.; Lehmann, A.; Mattsson, J. P.; Nilsson, K.; Sundén, G.; Swanson, M.; von Unge, S.; Woo, A. M.; Wyle, M. J.; Zheng, X. J. Med. Chem. 2008, 51, 4315-4320
2. Korenkov, A. I.; Niendorf, W. R.; Darwish, N.; Glaeser, E.; Gaab, M. R. Neurosurg. Rev. 2002, 228-230
3. Raphael, J.; Leo, R. J.; Baer, D. Psychosomatics 2005, 503-507
4. Wirth, T. Microreactors in Organic Synthesis and Catalysis; Wiley-VCH: Weinheim, 2008
5. Hartman, R. L.; Jensen, K. F. Lab Chip 2009, 9, 2495-2507
6. Mason, B. P.; Price, K. E.; Steinbacher, J. L.; Bogdan, A. R.; McQuade, D. T. Chem. Rev. 2007, 107, 2300-2318
7. Geyer, K.; Gustafsson, T.; Seeberger, P. H. Synlett 2009, 15, 2382-2391
8. Baumann, M.; Baxendale, I. R.; Ley, S. V. Mol. Divers. 2011, 15, 613-630
9. Jähnisch, K; Hessel, V.; Löwe, H.; Baerns, M. Angew. Chem., Int. Ed. 2004, 43, 406-446
10. Luis, S. V.; Garcia-Verdugo, E. RSC Green Chemistry No. 5: Chemical Reactions and Processes under Flow Conditions; The Royal Society of Chemistry: London, 2010.
11. Wiles, C.; Watts, P. Micro Reaction Technology In Organic Synthesis; CRC Press: Boca Raton, FL, U.S.A. 2011.
12. Kirschning, A.; Solodenko, W.; Mennecke, K. Chem.-Eur. J. 2006, 12, 5972-5990
13. Wiles, C.; Watts, P. Eur. J. Org. Chem. 2008, 10, 1655-1671
14. Hartman, R. L.; McMullen, J. P.; Jensen, K. F. Angew. Chem., Int. Ed. 2011, 50, 7502-7519
15. Elebring, T.; Guzzo, P.; Holmen, A.; Olsson, T.; Swanson, M.; von Unge, S. New Aminopropylphosphinic Acids. PCT Int. Appl. WO 0142252, Priority Date Dec 9, 1999.
16. A Vapourtec R4/R2+ equipment with two or three pumps was used. For further information, see http://www.vapourtec.co.uk/.
17. The product 6 is somewhat volatile, and the slightly lower yield in comparison to that from the batch process is presumably due to coevaporation with toluene. For physical properties of 6, see: Zhang, D.; Yuan, C. Chem.-Eur. J. 2009, 15, 4088-4101
18. Chebib, M.; Kumar, R. J.; Johnston, G.; Hanrahan, J. Neurologically active compounds. PCT Int. Appl., WO 2006000043 A1, Priority Date Jan 5, 2006.
19. Fougére, C.; Erwann, G.; Hardouin, J.; Lecouvey, M. Eur. J. Org. Chem. 2009, 34, 6048-54
20. Back Pressure Controller from Syrris FRX system. For further information, see http://www.syrris.com.