Flow Chemistry: Continuous Synthesis and Purification of Pharmaceuticals and Fine Chemicals
Date: July 8-10, 2013 | Tuition: $2,200 | Continuing Education Units (CEUs): 1.5
For approximately two centuries, organic synthesis has generally been conducted in a batch mode (flasks, vessels). Currently, in contrast to nearly all other major manufacturing industries, pharmaceutical companies utilize batch approaches for synthesis, with few exceptions. As economic and environmental pressures have increased, so has interest in continuous processes and continuous manufacturing. Chemistry in flow provides exquisite control over reaction conditions, incorporates continuous separations and in-line recycling of reagents, and because reactor volumes are small compared to batch, significantly enhances safety. Scale-up to large production is achieved not with stepwise transitions to larger and larger vessels, but by knowledge based selection of the appropriate size, running multiple systems in parallel, and adjusting the time a system is in operation. Moreover, a much broader range of reaction conditions (temperature, pressure, and reaction time) and many classes of reactions that are impossible, hazardous, low-throughput, or capricious in batch are safely and conveniently achieved in flow.
This course will focus on the fundamental principles and technologies used in the continuous synthesis and purification of small molecules. The advantages and challenges of flow or continuous manufacturing in comparison to batch for the production of small molecules will be discussed extensively. Advanced topics will include automation, scale-up strategies, cutting-edge methods of synthesis, and purification. Those who complete this course will not only possess a thorough knowledge base, but also will be able to make informed, systematic decisions in selecting between continuous or batch methods for a particular situation or project.
Fundamentals: Core concepts, understandings and tools (30%)
Latest Developments: Recent advances and future trends (25%)
Industry Applications: Linking theory and real-world 30%)
Other: Decision making and designing for change (15%)
Lecture: Delivery of material in a lecture format (50%)
Discussion or Groupwork: Participatory learning (40%)
Labs: Demonstrations, experiments, simulations (10%)
Introductory: Appropriate for a general audience (10%)
Specialized: Assumes experience in practice area or field (70%)
Advanced: In-depth explorations at the graduate level (20%)
- Define fundamentals of continuous synthesis and purification.
- Incorporate state of the art flow technologies in discovery, development, and manufacturing.
- Design, analyze, and optimize multi-step continuous synthesis systems.
- Identify areas within flow synthesis and that require further research and development.
- Determine optimum synthesis, purification, and scaling strategy for a particular project.
Apply reaction engineering strategies to process development and optimization.
Who Should Attend
This course is designed for scientists and engineers in pharmaceutical and fine chemicals research, development, and manufacturing. The course will be of particular benefit to chemists and chemical engineers who are or are considering implementing continuous flow synthesis into their programs. Those who should attend include:
- Chemists (Discovery/Medicinal and Process Development) and Chemical Engineers in pharmaceutical and fine chemicals research and development
- Chemists and Chemical Engineers in pharmaceutical and fine chemicals manufacturing
- Managers responsible for pharmaceutical fine chemicals research, development, and manufacturing
Session 1--1.5 hours
Introduction: Flow Chemistry, definitions, strategy, state-of-the-art (Jamison)
Session 2--1.5 hours
Flow chemistry – a literature survey (Jamison)
Session 3--1.5 hours
Reaction engineering principles for continuous flow synthesis (Jensen)
Session 4--1.5 hours
Multiphase reaction systems – reaction engineering principles (Jensen)
Session 5--1.5 hours
Reactions at extreme conditions and handling of unstable intermediates (Jamison)
Session 6--1.5 hours
Catalysis in flow (Jamison)
Session 7--1.5 hours
Continuous separation techniques (work-up) (Jensen)
Session 8--1.5 hours
Continuous separation - Solids handling in flow (Jensen)
Session 9--1.5 hours
Multistep synthesis strategies (Jamison)
Session 10--1.5 hours
Design, scaling, and optimization of flow processes (Jensen)
Session 11--1.5 hours
Summary cases studies, outlook, problems from audience, and lab tours (Jamison and Jensen)
Course schedule and registration times
Class runs 9:00 am - 5:00 pm each day.
9:00 am - 10:00 am - Session
10:00 am - 10:30 am - Break
10:30 am - 12:00 pm - Session
12:00 pm - 1:30 pm - Lunch
1:30 pm - 3:00 pm - Session
3:00 pm - 3:30 pm - Break
3:30 pm - 5:00 pm - Session
Registration is on Monday morning from 8:15 - 8:45 am.
Special events include a dinner for course participants and faculty on Monday night. Evening activities are included in tuition.
About the Lecturers
Timothy F. Jamison is a Professor of Chemistry at the Massachusetts Institute of Technology. He was born in San Jose, CA and grew up in neighboring Los Gatos, CA, and graduated from the University of California, Berkeley (B.S., Chemistry). While at Berkeley he conducted undergraduate research with Professor Henry Rapoport for nearly three years. Thereafter, a Fulbright Scholarship supported ten months of research in Professor Steven A. Benner’s laboratories at the ETH in Zürich, Switzerland. As an NSF Graduate Fellow at Harvard University, his Ph.D. research with Professor Stuart L. Schreiber was in the general area of target-directed synthesis. As a Damon Runyon-Walter Winchell postdoctoral fellow in the laboratory of Professor Eric N. Jacobsen (Harvard University), he developed enantioselective catalytic reactions and utilized them in target-directed synthesis. In July 1999, he began his independent career at MIT, where his research interests are broadly based in chemical synthesis (batch and flow), primarily in the development of new methods of organic synthesis and their implementation in target-directed synthesis. As a Co-PI in the Novartis-MIT Center for Continuous Manufacturing he focuses on using the capabilities and principles of flow synthesis to not only streamline chemical synthesis, but also to discover new chemical reactions that are either not possible or not suited to batch synthesis.
Klavs F. Jensen is Warren K. Lewis Professor and Head of the Chemical Department at the Massachusetts Institute of Technology. He received his M.Sc. in Chemical Engineering from the Technical University of Denmark and his Ph.D. from the University of Wisconsin-Madison. He has conducted independent research in reaction engineering since 1980 and addressed a wide range of processes, including energy conversion technologies, heterogeneous catalysis, reactive processing of thin films for electronic and optical devices, and most recently, continuous synthesis and purification technologies for fine chemical and pharmaceuticals. He has worked in miniaturized flow system for chemical synthesis and separations since the late 1990s. Catalysis, chemical kinetics and transport phenomena related to processing of materials for biomedical, electronic, energy conversion, and optical applications also remain topics of interest along with development of simulation approaches for reactive chemical systems. As a Co-PI in the Novartis-MIT Center for Continuous Manufacturing he focuses on novel reaction and work-up techniques. He is the co-author of more than 450 journal and conference publications as well as several edited volumes and 25 US patents. He serves on advisory boards to universities, companies, professional societies, and governments. He is the recipient of several awards, including a National Science Foundation Presidential Young Investigator Award, a Camille and Henry Dreyfus Foundation Teacher-Scholar Grant, a Guggenheim Fellowship, and the Allan P. Colburn, Charles C.M. Stine, and R.H. Wilhelm Awards of the American Institute of Chemical Engineers. Professor Jensen is a member of the U.S. National Academy of Engineering and the American Academy of Arts and Science. He is also a Fellow of the American Association for the Advancement of Science (AAAS), the American Institute of Chemical Engineers, and the Royal Society of Chemistry.
This course takes place on the MIT campus in Cambridge, Massachusetts. We can also offer this course for groups of employees at your location. Please contact the Short Programs office for further details.
Links & Resources
- MIT’s Prof. Klavs Jensen Wins IUPAC-ThalesNano International Prize For Outstanding Work In Flow Chemistry
- Continuous drug manufacturing offers speed, lower costs - New system developed by MIT researchers could help transform the pharmaceutical industry
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