Trouble with potassium carbonate and centrifuges: Mass transfer and scale-up effects in the manufacture of ZD9331 POM quinacetate

Organic Process Research and Development

Volumn 10, Issue 1, 2006, Pages 153-158

  Moseley, Jonathan D ^a   Bansal, Parminder ^a   Bowden, Sharon A ^a   Couch, A Edward M ^a   Hubacek, Ivo ^b   Weingärtner, Günter ^b  

^a ASTRAZENECA   (United Kingdom)

^b Dottikon Exclusive Synthesis AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 33344464697     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op0501693     Document Type: Article

References (21)

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14. Zeneca internal 6-monthly reports: Warren, K. E. H. February 1994-March 1998 and Horbury, J. September 1998-March 1999.
15. Initial investigations conducted by John Horbury, Richard Wisedale and Claire Ancell.
16. The four pilot batches were combined into a single batch for convenience due to the size of the dryer. Analysis of individual batch 1 prior to drying showed that it would comfortably have passed the specification for O-POM quinacetate and inorganic content.
17. Atherton, J. H.; Carpenter, K. J. Process Development: Physicochemical Concepts; Oxford University Press: Oxford, 1999.
18. Zweitering T. N. Chem. Eng. Sci. 1958, 8, 244-253.
19. Custers, J. P. A.; Hersmis, M. C.; Meuldijk, J.; Vekemans, J. A. J. M.; Hulshof, L. A. Org. Process Res. Dev. 2002, 6, 645-651.
20. An analysis of the damp weights discharged from the centrifuge for both portions of batches 1-3 indicated that the second portion was significantly heavier than the first one, probably because of discharging a slurry. Consequently, the second portion contained a greater mass of O-POM quinacetate that was subjected to the same wash volume as the first portion, hence, the probable cause of the failure. The fact that both portions of batch 2 passed specification indicates the wash process was not far from successful conditions, but it would not have been very robust.
21. Both portions of each batch were reprocessed together to simplify the batch histories, even though their first portions had been within specification.