Scalable Green Chemistry Case Studies from the Pharmaceutical Industry

Introduction to Green Pharmaceutical Science: Fact, Fiction, and Future, Julie B. Manley

Green Chemistry in Drug Development, Apurba Bhattacharya, Siddhartha Akasapu, and Rakeshwar Bandichhor
Introduction
Aprepitant
Paroxetine
Pregabalin
Sertraline
Conclusions

Development of Green-by-Design, Practical Biocatalytic Processes, Gjalt W. Huisman and Steven J. Collier
Introduction
Introduction on Biocatalysis and Directed Evolution
Biocatalysis and Green Chemistry
Ketoreductase Processes for Chiral Alcohols
Transaminase Processes to Chiral Primary Amines
Acyltransferase Approach to Simvastatin
Integrated Biocatalytic Processes
Conclusions and Outlook

Application of Green Metrics to Scalable Industrial Synthesis Plans: Approaches to Oseltamivir Phosphate (Tamiflu R _), John Andraos
Introduction
Green Metrics Essentials for Industrial Chemists
Oseltamivir Approaches: Synthesis Strategies
Oseltamivir Syntheses: Material Efficiencies
Concluding Remarks

The Road to Becoming Green: Process Development of AR-A2, an Active Pharmaceutical Ingredient with Antidepressant Activity, Hans-J¨urgen Federsel, Martin Hedberg, Fredrik R. Qvarnstr¨om, and Wei Tian
The Green Agenda
Starting the New Project
Time for Change: The Road Map to Better Synthesis
Homing in on Safety, Health, and Environment (SHE) Improvements
Focusing the Morpholinobenzoic Acid Side Chain: Design of the Ultimate Process
Reaching the End Product: SHE Perspective on the Final Stages
Summary: Improvements in Environmental Impact of the AR-A2 × HBr Process

Improved and Greener Process for Pioglitazone and Its Pharmaceutically Acceptable Salts, Apurba Bhattacharya, Rakeshwar Bandichhor, and Lokeswara Rao Madivada
Introduction
A Green Attitude
Synthesis of Pioglitazone
Development of a Greener Process: Improved Process for Pioglitazone
Process Optimization
Conclusions

The Development of a Convergent Green Synthesis of Linezolid, an Oxazolidinone Antibacterial Agent, William R. Perrault, James B. Keeler, William C. Snyder, Christian L. Clark, Michael R. Reeder, Richard J. Imbordino, Rebecca M. Anderson, Nabil Ghazal, Stephen L. Secreast, and Bruce A. Pearlman
Background
Green Linezolid Process
Conclusion

Development of a Nonaqueous Process for the Synthesis of 3-Amino-pentan-1,5-diol, Thimma Rawalpally and Thomas Cleary
Introduction
IND Synthesis
First-Generation Aminodiol Synthesis
Second-Generation Synthesis
Environmental Assessment of the Synthetic Routes

Development of a Robust, Environmentally Responsible Process for the Manufacture of Tofacitinib Citrate, Rajappa Vaidyanathan
Introduction
Retrosynthetic Strategy
Approaches to Piperidine 6
Choice and Synthesis of the Coupling Partner
The Debenzylation Step
Amidation, Salt Formation, and Isolation
Conclusions

Selective Nitration under cGMP Conditions, Peter Poechlauer, Sascha Braune, and Roland Oberm¨uller
Introduction: Pharmaceuticals—Successful Products, Inefficient Manufacture?
Pharmaceutical Production
Process Intensification
Process Intensification in Practice
Safety First: A thorough Analysis
Consequences for Plant Design
Quality
Continuous Improvement and Its Consequences on the Environmental Impact of a Plant
Conclusion

Going Green Using Combined Real-Time Analytics and Process Automation, Dominique Hebrault and Terry Redman
Introduction
Case Studies
General Conclusions

Approaches to the Scale-Up of Organic Chemistry Using Microwave Heating, Nicholas E. Leadbeater
Introduction
Scale-Up of Chemistry Performed Using Microwave Heating
Concluding Remarks

Challenges Faced and Future Directions, Stefan G. Koenig
Introduction
Successful Beginnings
The Future of Green Chemistry
Conclusions Index 357

Biography

Stefan Koenig received his PhD from Yale University before conducting postdoctoral research at the ETH (Swiss Federal Institute) in Zurich, Switzerland. He embarked on his professional career in the pharmaceutical industry at Sepracor (now Sunovion Pharmaceuticals). Currently, he is a scientist at Genentech and chair of Roche/Genentech’s global Green Chemistry Technical Working Group.

"At last! A book which provides a discussion of green chemistry from a process chemistry/engineering viewpoint. The case studies on individual pharmaceuticals in the various chapters are supplemented by a great general introductory chapter and a final concluding chapter by the editor."
--Dr. Trevor Laird, Editor, Organic Process Research & Development

"This monograph is a tutorial featuring not only an impressive overview of the virtues of green chemistry, but also real-world cases that illustrate how this emerging field can be applied within the pharma arena to great economic, as well as environmental, advantage."
--Prof. Bruce H. Lipshutz, University of California, Santa Barbara, USA

"This thirteen-chapter book summarizes the most recent green chemistry and engineering achievements in the pharmaceutical industry. It provides good examples that illustrate the concept of green-by-design, the practice of green metrics, and the advancement of green technologies in drug design, development and production."
--Prof. Wei Zhang, University of Massachusetts Boston, USA

"Scalable Green Chemistry represents an important and timely contribution to the armamentarium of the pharmaceutical green chemist. This book’s case studies, contributed by well-known and highly respected authors from this field, will be catalysts for the progression and broader adoption of a more sustainable way to do drug synthesis and manufacture."
--Dr. Berkeley W. Cue, Jr., BWC Pharma Consulting LLC, USA

"This timely book illustrates the application of green chemistry principles to several prominent cases in greener pharmaceutical manufacturing. It showcases excellent examples of the impact of green chemistry on the pharmaceutical industry."
--Prof. Chao-Jun Li, McGill University, Canada