Synthetic toolbox: Route selection

Summary and further reading

Route selection is at the foundation of designing a route that meets operational, environmental, legal and economic factors. The following are a selection of just some of the tools that are available to provide information and assistance with route selection:

These tools enable information to be sourced for route selection: ranging from searching for existing synthesis routes to an API; information and physical data on existing intermediate compounds; reagents and transformations; patents and even designing novel synthetic routes to a given target molecule. 

Recommended reading:

There are also a wealth of journal articles and printed books on the subject. Here is a selection for further reading:

P. J. Dunn, The importance of Green Chemistry in Process Research and Development, Chem. Soc. Rev., 2012, 41, 1452-1461.

R. B. Leng, M. V. M. Emonds, C. T. Hamilton and J. W. Ringer, Holistic Route Selection, Org. Process Res. Dev., 2012, 16, 415-424. 

R. Dach, J. J. Song, F. Roschangar, W. Samstag and C. H. Senanayake, The Eight Criteria Defining a Good Chemical Manufacturing Process, Org. Process Res. Dev., 2012, 16, 1697-1706. 

M. Butters, D. Catterick, A. Craig, A. Curzons, D. Dale, A. Gillmore, S. P. Green, I. Marziano, J. - P. Sherlock and W. White, Critical Assessment of Pharmaceutical ProcessesA Rationale for Changing the Synthetic Route, Chem. Rev., 2006, 106, 3002-3027.

I. W. Davies and C. J. Welch, Looking Forward in Pharmaceutical Process Chemistry, Science, 2009, 325, 701-704. 

H. - J. Federsel, Chemical Process Research and Development in the 21st Century: Challenges, Strategies, and Solutions from a Pharmaceutical Industry Perspective, Acc. Chem. Res., 2009, 42, 671-680.

N. G. Anderson, Assessing the Benefits of Direct Isolation Processes, Org. Process Res. Dev., 2004, 8, 260-265. 

A. A. Desai, E. J. Molitor and J. E. Anderson, Process Intensification via Reaction Telescoping and a Preliminary Cost Model to Rapidly Establish Value, Org. Process Res. Dev., 2012, 16, 160-165.

G. Van der Vorst, W. Aelterman, B. De Witte, B. Heirman, H. Van Langenhove and J. Dewulf, Reduced resource consumption through three generations of Galantamine[middle dot]HBr synthesis, Green Chem., 2013, 15, 744-748.

C. A. Busacca, D. R. Fandrick, J. J. Song and C. H. Senanayake, The Growing Impact of Catalysis in the Pharmaceutical Industry, Adv. Synth. Catal., 2011, 353, 1825-1864.

T. Y. Zhang, Process Chemistry:  The Science, Business, Logic, and Logistics, Chem. Rev., 2006, 106, 2583-2595.

C. - K. Chen and A. K. Singh, A “Bottom-Up” Approach to Process Development:  Application of Physicochemical Properties of Reaction Products toward the Development of Direct-Drop Processes, Org. Process Res. Dev., 2001, 5, 508-513.

P. J. Dunn, Pharmaceutical Green Chemistry process changes - how long does it take to obtain regulatory approval?, Green Chem., 2013, 15, 3099-3104.

K. D. Collins and F. Glorius, A robustness screen for the rapid assessment of chemical reactions, Nat. Chem., 2013, 5, 597-601.

Bretherick's Handbook of Reactive Chemical Hazards, 2006, 2.

J. Blacker and M. T. Williams, Pharmaceutical Process Development : Current Chemical and Engineering Challenges, Royal Society of Chemistry, Cambridge, 2011.