Flow Chemistry: Continuous Synthesis and Purification of Pharmaceuticals and Fine Chemicals
Date: This course will run in 2017 | Tuition: TBD | Continuing Education Units (CEUs): TBD
*This course has limited enrollment. Apply early to guarantee your spot.
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 primarily utilize batch approaches for synthesis. 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 multistep continuous synthesis systems.
- Identify areas within flow synthesis 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 and Jensen)
Session 2--1.5 hours: Lab tours to see flow chemistry instrumentation
Session 3--1.5 hours: Flow chemistry–a literature survey (Jamison)
Session 4--1.5 hours: Reaction engineering principles for continuous flow synthesis (Jensen)
Session 5--1.5 hours: Multiphase reaction systems–reaction engineering principles (Jensen)
Session 6--1.5 hours: Reactions at extreme conditions and handling of unstable intermediates (Jamison)
Session 7--1.5 hours: Catalysis in flow (Jamison)
Session 8--1.5 hours: Continuous separation techniques (work-up) (Jensen)
Session 9--1.5 hours: Continuous separation–solids handling in flow (Jensen)
Session 10--1.5 hours: Multistep synthesis strategies (Jamison)
Session 11--1.5 hours: Design, scaling, and optimization of flow processes (Jensen)
Course schedule and registration times
Registration is Monday morning, 8:15 - 8:45 am.
Class runs 9:00 am - 5:00 pm Monday and Tuesday and 9:00 am - 3:15 pm on Wednesday.
Special events include a dinner for course participants and faculty on Monday night. Evening activities are included in tuition.
senior research scientist, university of mississippi
"It's a wonderful opportunity for every chemist to understand the new trends in chemical synthesis and manufacturing."
senior principal chemist, w.r. grace and company
"I would highly recommend it to colleagues involved in synthesis and scale up."
director of research, regis technologies, inc.
"Excellent presentation of material and structure of the course, highly engaging, super informative. The course is an excellent start for the beginners and a perfect tune-up for those with moderate flow chemistry experience."
process engineer, hospira
"The course was technical, relevant to topic, and had an industry focus with application of new technology... as promised. It was a nice balance between theory from an engineering perspective and application from the chemist's lab."
"The instructors presented an excellent theoretical foundation to the subject along with current, relevant case studies of the technology in practice. It is an excellent course for those who need to become familiar with flow chemistry but have little or no practical experience. At the same time, there was sufficient depth such that it was also highly useful to someone already familiar with the field."
About the Lecturers
Timothy F. Jamison is a Professor of Chemistry at the Massachusetts Institute of Technology. He 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 10 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 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 Engineering 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 U.S. 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 complete the Custom Programs request form 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
- Putting the squeeze on cells - By deforming cells, researchers can deliver RNA, proteins and nanoparticles for many applications.