Practical Process Research and Development

Bringing a compound to market quickly and profitably requires efficient and

cost-effective processes for preparing large amounts of the target compound

and intermediates. The key to rapid and successful process development is avoiding scale-up problems. However, an understanding of scale-up issues is rarely

taught in academia and may take years of industrial experience to acquire.

Practical Process Research & Development teaches how to anticipate and

avoid these problems when processes are being scaled up from the research lab or

pilot plant. The approach is pragmatic, with a minimum of theory and over

100 practical scale-up tips. Many tables and detailed reaction schemes

allow the reader to identify critical processing steps quickly. This

practical guide is essential reading for chemists and chemical engineers

involved in industrial process research and/or process development and for

anyone seeking a clearer understanding of how and why process R&D is conducted in the pharmaceutical and fine chemicals industries.

KEY FEATURES

· Provides insights into generating rugged, practical, cost-effective

processes for the chemical preparation of "small molecules"

· Breaks down process optimization into route, reagent, and solvent

selection, development of reaction conditions, workup, crystallizations, and more

· Describes how to anticipate and avoid difficulties in scaling up reactions

· Discusses guidelines for the timely development of processes

· Illuminates principles with examples from the recent literature

· Includes over 100 tips for rapid process development

· Presents guidelines for implementing and troubleshooting processes

· Written by an author with over 22 years experience in process R&D in

the pharmaceutical industry

"... A must reference on every process chemists (both the novice and the experienced practitioner) desk. This will be required reading by all new chemists, engineers and analysts in my department."

--Sean T. Nugent, Searle Research & Development

"Neal Anderson has assembled an immense amount of practical information that is absolutely essential to the design and execution of safe, reliable, efficient large-scale syntheses. Critical facts once hidden in obscure sources or chemical folklore are now organized for ready access. Countless illustrative reactions and sequences from the latest literature are discussed lucidly, and impress upon the reader the scope and sophistication of modern organic process chemistry. This book is a must for beginners and old hands alike."

- Raymond Conrow, Assistant Technical Director, Chemical Preparations Research, Alcon Laboratories

"Perhaps the highest praise one can give this book is to say that the Foreword by Barry Sharpless raises very high expectations...and the book meets and at times exceeds those expectations."

- Organic Process Research & Development

beginners and old hands alike."

- Raymond Conrow, Assistant Technical Director, Chemical Preparations Research, Alcon Laboratories

"Perhaps the highest praise one can give this book is to say that the Foreword by Barry Sharpless raises very high expectations...and the book meets and at times exceeds those expectations."

- Organic Process Research & Development

This book provides a comprehensive, step-by-step approach to organic process research and development in the pharmaceutical, fine

chemical, and agricultural chemical industries. Process R&D describes the steps taken, following synthesis and evaluation, to bring key

compounds to market in a cost-effective manner. More people are being hired for work in this area as increasing numbers of drug candidates are

identified through combinatorial chemistry and high-throughput screening. The book is directed to industrial (primarily organic) chemists, and

academicians (particularly those involved in a growing number of start-up companies) and students who need insight into industrial process R&D. Current books do not describe hands-on, step-by-step, approaches to solving process development problems, including route, reagent,

and solvent selection; optimising catalytic reactions; chiral syntheses; and "green chemistry." "Practical Process Research and Development" will be a valuable resource for researchers, managers, and graduate students.

* Provides insights into generating rugged, practical, cost-effective processes for the chemical preparation of "small molecules"

* Breaks down process optimization into route, reagent and solvent selection, development of reaction conditions, workup, crystallizations and more

* Includes over 100 tips for rapid process development

* Presents guidelines for implementing and troubleshooting processes

tment."

--Sean T. Nugent, Searle Research & Development

aration of "small molecules"

· Breaks down process optimization into route, reagent, and solvent

selection, development of reaction conditions, workup, crystallizations, and more

· Describes how to anticipate and avoid difficulties in scaling up reactions

· Discusses guidelines for the timely development of processes

· Illuminates principles with examples from the recent literature

· Includes over 100 tips for rapid process development

· Presents guidelines for implementing and troubleshooting processes

· Written by an author with over 22 years experience in process R&D in

the pharmaceutical industry

"... A must reference on every process chemists (both the novice and the experienced practitioner) desk. This will be required reading by all new chemists, engineers and analysts in my department."

--Sean T. Nugent, Searle Research & Development

d analysts in my department."

--Sean T. Nugent, Searle Research & Development

Neal G. Anderson, Ph.D., has worked for over 20 years in chemical process R&D in the pharmaceutical industry. He earned a B.S. degree from the University of Illinois and a Ph.D. in medicinal chemistry from the University of Michigan and completed post-doctoral studies at McNeil Laboratories. With almost 18 years in process R&D at Bristol-Myers Squibb Co. in New Brunswick, New Jersey, Dr. Anderson has extensive hands-on experience in the laboratory, pilot plant, and manufacturing facilities. He has made key contributions to processes for the manufacture of four major drug substances, including captopril, and has participated in 12 manufacturing start-ups and successfully introduced many processes to pilot plants. He received the Bristol-Myers Squibb President's Award and spot awards, and his final position was Principal Scientist.In 1997, Dr. Anderson established Process Solutions L.L.C., a consulting firm offering practical guidance on developing and implementing processes for bulk pharmaceuticals and fine chemicals. As part of these consulting services, he presents courses on selected aspects of practical process R&D.

Neal G. Anderson, Anderson's Process Solutions LLC, Jacksonville, Oregon, USA

Foreword by K. Barry Sharpless. Foreword by Jerome L. Moniot. Preface. About the Author. Approaches to Process Development. Route Selection. Reagent Selection. Solvent Selection. Running the Reaction. Effects of Water. In-Process Controls. Optimizing the Reaction by Minimizing Impurities. Optimizing Catalytic Reactions. Work-Up. Tools for Purifying the Product: Column Chromatography, Crystallization, and Reslurrying. Final Product Form and Impurity Considerations. Vessels and Mixing. Preparing for and Implementing the Scale-up Run. Troubleshooting. Chiral Syntheses. General Index. Reaction Type Index. Reagent Index.