David Ford, Ph.D. Mettler Toledo Autochem Symposium June 21, 2017 Cambridge, MA
|
|
- Zoe Heath
- 5 years ago
- Views:
Transcription
1 David Ford, Ph.D. Mettler Toledo Autochem Symposium June 21, 2017 Cambridge, MA
2 Snapdragon Chemistry Snapdragon Chemistry was created to deliver complete flow chemistry solutions to clients. Using advanced continuous manufacturing technology, we are helping our clients to Improve access to existing molecules Reduce safety and environmental risks Enable new chemistries for manufacture Discover new molecules Process Development Technical Consulting Flow Chemistry CRO Custom Building Blocks Product Delivery 2
3 Batch vs. Flow Chemistry Flexible lots of installed capacity Difficult to scale from lab to plant Difficult to model computationally Significant safety risks Poor control over process parameters Limited range of temp & pressure Fixed output Purpose-built inexpensive (disposable reactor) for given reaction Easy to scale from lab to plant Can be modeled computationally Inherently safer Exquisite control over process parameters Broader range of temp & pressure Flexible output with same reactor 3
4 Is flow chemistry new? Flow chemistry is a new and exciting way to think about developing reactions! Chemical engineers have been running continuous processes since the dawn of time! 4
5 Continuous vs. flow chemistry Continuous production Always affords incremental efficiency gains compared to an analogous batch process Save time on start-up and shutdown Less material at risk Limited inventory of hazardous chemicals or reaction mixtures Compact apparatus Opportunity for excellent process control Flow chemistry Flow chemistry is chemistry that is only practical as a continuous process We use detailed knowledge of the chemical process to produce results that would be difficult to impossible to replicate in batch Mixing sensitivity Precise timing Extreme pressures and temperatures Very hazardous conditions The equipment of continuous production allows us to access new chemical space (i.e. flow chemistry)! Snapdragon works on projects in both categories! 5
6 Evolution from Simple to Complex Molecules 24 x8 x8 Acrylic acid production Decades old process Simple, 3 carbon molecule Prepared in one step from propylene feed >5 million tons per year Novartis-MIT Redline Project Reported in 2013 One drug product Integrated synthesis and formulation 3 chemical steps, isolations and formulation Angew. Chem. Int. Ed. 2013, 52, x2 x6 Darpa-MIT POD Reported in 2016 Seven drug products Integrated synthesis and formulation Multiple chemical steps, isolations and formulation Science, 2016, 6281,
7 Chemistry investment Evolution of flow chemistry toward general platforms Opportunity: rapid development with tools that are broadly applicable Pharma continuous manufacturing process (GMP) Minimal engineering investment to adapt to a new process Commodity chemical manufacturing Engineering investment 7
8 Snapdragon areas of expertise Ultrafast reactions Static Mixer Characterization Mixing time vs Total Flow Rate High temperature/high pressure reactions mixing completion time (ms) 1/8" mixer 5000 (100 g/h) 3/8" mixer (>5 kg/h) 500 1/4" mixer (1-5 kg/h) Operating range ( 200 ms) Flow rate (ml/min) Temp > 200 C Pressure > 1000 psi Gas/liquid reactions Flow Photochemistry ( 1 O 2, photoredox etc) Electrochemistry Fixed bed catalysis 8
9 Fast reactions Prototypical reactions are lithiations Batch processes often are often run at cryogenic temperatures. Why? Two major drivers: Mixing sensitivity Heat transfer Continuous processes can offer scalable mixing and heat transfer Added benefit: all of the other advantages of continuous processing! 9
10 Heat transfer Q = U A ΔT Heat transfer coeff (materials of construction) Surface area Temp. diff. across jacket As we scale up in a batch reactor, volume scales as r 3, but area only scales as r 2 decreasing surface area per unit volume for heat transfer In a tubular reactor, area and volume can scale together by using longer tubes or by using parallel tubes If we can t remove the heat quickly enough, we need to cool the reactor down to prevent the temperature from getting too high 10
11 Mixing sensitivity in batch RLi RLi SM Product Impurity RLi dosing High [RLi] SM in soln High [SM] Impurity formation Mixing rate needs to be faster than reaction rate! Solution: slow down the chemistry or speed up the mixing. We cool the reaction to buy ourselves time to mix. 11
12 Mixing sensitivity in flow RLi RLi SM Product Impurity SM in soln Smooth Fast mixing (static mixer) Smooth Slow mixing (laminar flow) Unsteady stoichiometry (pulsation) Trouble! RLi dosing 12
13 Where and how do we use FlowIR? Where: pretty much everywhere - Reagent stock solution stability - Gas dissolution in flow - Reactive intermediate stability and tracking - Tracking flow reaction steady state - Product process optimization and characterization How: Peel FlowIR multi-layer information - Chemometrics analysis of solvent composition - Quantification of starting material and product (IC Quant.) - Programmed FlowIR titration Starting materials intermediate product 13
14 Real-time reaction monitoring Need on-line PAT to gain reaction insight Low-maintenance and robust - No need for liquid nitrogen cooling: rarely turned off - No N 2 purge, no alignment - Small footprint Small sample size - 20 or 50 µl flow cell - Auxiliary flow cell heater and temp controlled - Microscale reaction in flow cell (sealed reactor) - stability studies - rapid reaction screening - reaction kinetics studies at variable temp 14
15 FlowIR Data Provides Diagnosis of Issues Chemometrics data processing Inconsistent results from aliquot sample and bulk collected sample Lower conversion found in bulk collected material FlowIR data shown repeated spiking pattern Chemometrics analysis enhanced the resolution 2.5 min intervals Glitch in Pump A delivery of n-buli explains observation of un-converted ArBr 15
16 Pressure (PSI) Pressure (PSI) Pump Performance Evaluation using Pressure Monitoring Pump A: reciprocating syringe pump with motor-driven switching valve Pressure Monitoring with Pump A Pump X: piston pump Pressure Monitoring with Pump X 30 8 ml/min 30 8 ml/min ml/min 20 6 ml/min 15 4 ml/min 15 4 ml/min ml/min difference drop (PSI) ml/min difference drop (PSI) Switching to pump X resolved the issue Smooth flow needs to be verified in the lab for mixing-sensitive reactions!
17 Case Study: A Practical Asymmetric Propargylation Original Chemistry: Boc H N Me O OMe Scale up of med chem process in batch failed Chiral epoxide synthesis required multiple steps, challenging chemistry TMS acetylene expensive raw material driving up cost of intermediate Snapdragon Proposal: BocHN Me O Li TMS Me 2 AlCl Boc H N Me OH TMS Project Goals: Ligand controlled propargylation using allene as starting material Scalable asymmetric process delivering better than 10:1 diastereoselectivity Hui Li, Jill Sheeran, Andy Clausen, Eric Fang, Matt Bio, Scott Bader Angew. Chem. Int. Ed. doi: /anie
18 Using FlowIR to Determine Gas Concentration in Pressurized Flow Reactor >2.5M solution in flow at 40 psi Allene saturated in THF at 1 atm RT 18
19 Ln [rel. Li-R] Stability of Lithium Allene? Decomposition follows 1 st order kinetics k = min -1, t 1/2 = C Organolithium Decay Kinetics y = x R² = Time (min) 19
20 Study of Lithiation Stoichiometry in Flow Efficient formation of lithioallene Precipitation risk beyond 0.7 equiv. HexLi 20
21 Importance of Mixing on Lithiation Static mixer was stable for short periods of time but failed due to precipitation of dilithioallene during extended operation Laminating mixers rapidly clogged 3D printed static mixer Laminating mixer Dynamic mixer gave stable performance without clogging for extended reaction times 21
22 Allenylzinc Screening and Optimization H N O H H C H ZnEt 2,R 2 N OH Li Chiral Ligands H H C H Zn O R 2 N Boc Me THF Boc H N Me OH 1-S,S + Boc H N Me OH 1-R,S N OH N L1, cinchonine N OH N L2, cinchonidine Ph NH 2 OH Ph L3 Me N OH Ph L4 N Me OH Ph Ph L5 Achiral Additives F 3 C OH A1 Me Me Me A2 OH O 2 N A3 OH Ph A4 OH A5 OH Me A6 OH Optimized conditions delivered 32:1 diastereoselectivity with 85% yield Li, H.; Sheeran, J.; Clausen, A. M.; Fang, Y.-Q..; Bio, M. M.; Bader, S. J. Angew. Chem. Int. Ed. 2017, in press 22
23 Optimized Propargylation Reactor Train 1905 cm -1 THF 1864 cm o C bath waste 1/8 OD tubing 30 mmol/hr = 15 grams/hr allene MFC FlowIR 20 psi BocHN Me CHO BocHN Me OH HexLi Zn* FlowIR CSTR Tube reactor Li Zn CSTR Tube Reactor 12.3 minutes 23
24 Optimized Propargylation Reactor Train Li Zn CSTR Tube Reactor 12.3 minutes 24
25 Case study: lithiation scale-up Challenge: lithiation reaction performed in batch with consistency issues, requires cryogenic conditions Evaluation in flow revealed that complete mixing in ~200 ms was required for acceptable product quality. Understanding the mixing allowed us to design and build a flow skid capable of performing the transformation at 1-2 kg/hour 25
26 Static mixers Static mixers provide efficient mixing without moving parts Characterized by Snapdragon using Bourne reactions and colorimetric readout of acid-base chemistry (publication forthcoming) Static mixers are critical for developing scalable processes with mixing-sensitive reactions! 26
27 Case Study: Rapid Scale-up by Design Lab to Plant by Calculation Static Mixer Characterization Mixing time vs Total Flow Rate mixing completion time (ms) 1/8" mixer (100 g/h) Flow rate (ml/min) 1/4" mixer (1-5 kg/h) Operating range ( 200 ms) 3/8" mixer (>5 kg/h) 27
28 Special opportunities afforded by fast reactions When we develop a process for a very fast reaction, the reactor can reach steady-state in just a few minutes It is practical to establish PAR and validate the process at full-scale using a modest amount of material In our case, ~15 minutes to establish stoichiometry PAR, and another ~15 minutes at the target conditions We can perform experiments using the unaltered >10 kg/day production process using only a few hundred grams of starting material! 28
29 Conclusions Continuous reactors afford us an exceptional degree of control over chemical processes, even in the most challenging cases Flow chemistry gives us the tools to reliably and safely perform chemistry that would be challenging or impossible in batch this allows chemists to think more creatively about new ways to assemble molecules PAT goes hand-in-hand with continuous: monitoring these processes gives valuable insights and in-process control Scale-up can be enabled through careful characterization of the reactor using model systems 29
30 Where do we go from here? Organic chemistry has lagged behind other fields in taking up new advances in data science One major challenge: we can t control batch processes well enough to collect good data! Continuous processes allow us the ability to precisely describe the conditions and collect high quality data Can we use this data combined with a deep understanding of our reactors to predictably and quickly scale up, scale down, and tech transfer? Can we leverage modern data science tools to develop chemical processes more rapidly? To lead us to better solutions? 30
31 Acknowledgements Matthew Bio Andrew Clausen Eric Fang Hui Li Jillian Sheeran Jade Nelson Scott Bader Adam Brown 31
Recent Advances to Improve Chemical Development
Recent Advances to Improve Chemical Development Agenda Challenges in Today s Pharma Industry Industry Drivers for Change Four Ways to Improve Organic Synthesis Enabling Technology Impact of New Tools on
More informationCONTINUOUS FLOW CHEMISTRY (PROCESSING) FOR INTERMEDIATES AND APIs
CONTINUOUS FLOW CHEMISTRY (PROCESSING) FOR INTERMEDIATES AND APIs Sripathy Venkatraman, Section Head at AMRI Abstract Many contract manufacturing organizations (CMOs) offer continuous flow chemistry, but
More informationLonza Factory of Tomorrow for Flow Processes and MicroReactors
Pharma&Biotech Lonza Factory of Tomorrow for Flow Processes and MicroReactors Practical Continuous Flow Technology, Munich, Germany Dominique Roberge / Lonza Ltd, 3930 Visp / 5 June 2013 Lonza Re-design
More informationIndustrial Applications of Microreactor Technology
Industrial Applications of Microreactor Technology Name / Lonza AG / xx Month 2010 Microreactors are at the heart of a dramatic shift in API production Microreactor (MR) technology enables continuous processes
More informationReferences. Continuous Manufacturing Process Development Plant Realizations. Microinnova Engineering GmbH. Europapark Allerheiligen bei Wildon
References Continuous Manufacturing Process Development Plant Realizations Microinnova Engineering GmbH Europapark 1 8412 Allerheiligen bei Wildon T +43 (0) 3182 62626-0 office@microinnova.com www.microinnova.com
More informationSupporting Information. Flow Grignard and Lithiation: Screening Tools and Development of Continuous Processes
for: Flow Grignard and Lithiation: Screening Tools and Development of Continuous Processes for a Benzyl Alcohol Starting Material Michael E. Kopach, *, Kevin P. Cole, Patrick M. Pollock, Martin D. Johnson,
More informationPerseverance. Experimentation. Knowledge.
2410 Intuition. Perseverance. Experimentation. Knowledge. All are critical elements of the formula leading to breakthroughs in chemical development. Today s process chemists face increasing pressure to
More informationon TM 2012 KinetiChem, Inc. Irvine, CA Jeffrey C. Raber, Ph.D.
Synthetr Synthetron TM on TM Flow Reactor Technology 2012 KinetiChem, Inc. Irvine, CA Jeffrey C. Raber, Ph.D. Flow chemistry offers significant advantages Current flow reactor technology does not meet
More informationProcess Safety. Process Safety and Hazard Assessment Avoiding Incidents in the Lab and in the Plant
Process Safety Process Safety and Hazard Assessment Avoiding Incidents in the Lab and in the Plant Process Safety Process Safety and Hazard Assessment From Early Development to Manufacturing The importance
More informationProcess Intensification
Process Intensification Adam Harvey Professor of Process Intensification Process Intensification Group Chemical Engineering & Advanced Materials Newcastle University, UK 30 th September 2014 History Pioneered
More informationMICROSTRUCTURE-BASED PROCESS ENGINEERING AND CATALYSIS
MICROSTRUCTURE-BASED PROCESS ENGINEERING AND CATALYSIS 1 2 APPLICATION PORTFOLIO Fine chemistry We design chemical processes from lab to pilot scale in a safe, efficient and flexible way: using micro-
More informationAsia Flow Chemistry System
Asia Flow Chemistry System Flow Chemistry Continuous Flow Synthesis of Carboxylic Acids from Grignard Reagents with Carbon Dioxide Gas MAR-000289 Version: 1.1 Issue date: 11/05/2016 Author: Andrew Mansfield
More informationContinuous, efficient multistage extraction
Continuous, efficient multistage extraction Andrea Adamo Zaiput Flow Technologies Department of Chemical Engineering, MIT Munich 01 February 2017 Back ground - MIT s efforts in continuous manufacturing
More information2nd International Symposium on Continuous Manufacturing of Pharmaceuticals
Aaron Beeler September 27, 2016 How Chemistry is Changing Small Molecule Manufacturing by Expanding the Reaction Toolbox 2nd International Symposium on Continuous Manufacturing of Pharmaceuticals http://www.beelerlab.com/
More informationContinuous Manufacturing: Process Intensification Strategies in Synthesis, Workup and Formulation with a special focus on solids
Continuous Manufacturing: Process Intensification Strategies in Synthesis, Workup and Formulation with a special focus on solids Dr. Dirk Kirschneck, Microinnova Engineering GmbH Content Microinnova Overview
More informationGreen Chemistry & Engineering for Pharmacuetical Industry Impact of Process Research / Route Scouting towards the Environment during API Life Cycle
Green Chemistry & Engineering for Pharmacuetical Industry Impact of Process Research / Route Scouting towards the Environment during API Life Cycle Dhileep Krishnamurthy, Ph.D. Outline Introduction Green
More informationApplications of the Micro Reaction Calorimeter
Applications of the Micro Reaction Calorimeter Power-compensation method. Versatility Automated sample addition, repeated or timed. Wide temperature range Pressure measurement Stirring Highly sensitive
More informationAttributes of Real time Micro Analytical Systems to Fully Exploit the Potential of Microscale Processing. Ray Chrisman, University of Washington, USA
Attributes of Real time Micro Analytical Systems to Fully Exploit the Potential of Microscale Processing Ray Chrisman, University of Washington, USA Definition of real time chemical analyzer A device that
More informationContinuous Flow for APIs and Intermediates (Part 1 of 2)
Continuous Flow for APIs and Intermediates (Part 1 of 2) A Cambrex webinar overview Nadim Kayaleh Senior Scientist The introduction of continuous flow processing has changed the way we conduct chemistry.
More informationContinuous Flow Reactions. From idea to production size scale up in 3 steps
Continuous Flow Reactions From idea to production size scale up in 3 steps PIN NL Spring Session 13 04 2017 13 4 2017 PIN NL Spring Session 1 Topics Introduction Flowlink Continuous Flow Reactions What
More informationElectronic Supplementary Information
Electronic Supplementary Material (ESI) for RSC Advances. This journal is The Royal Society of Chemistry 2014 S1 Electronic Supplementary Information Flash Carboxylation: Fast Lithiation - Carboxylation
More informationAdvanced Flow Reactors Teaming up Chemistry and Chemical Engineer Greener Processes and Improved Economics. Frank Schmidt Sales Director
Advanced Flow Reactors Teaming up Chemistry and Chemical Engineer Greener Processes and Improved Economics Frank Schmidt Sales Director Evolution (Revolution) in Chemical Processing 2 Cost Batch process
More informationLABOTRON EXTRACTION & SYNTHESIS 2450 MHz
LABOTRON EXTRACTION & SYNTHESIS 2450 MHz The LABOTRON TM series is the generic name for a ground breaking range of integrated reactor and microwave transmission systems especially designed to carry out
More informationReturn on Investment in Discovery Chiral Separations
Return on Investment in Discovery Chiral Separations Averica Discovery Services 260 Cedar Hill Street Marlborough MA 01752 www.avericadiscovery.com @averica_feed What Should I Spend? Understanding ROI
More informationProcess Development & Scale-Up of the AIR Technology
Process Development & Scale-Up of the AIR Technology Lloyd Johnston, Ph.D. Vice President of Process Development & Manufacturing October 6, 2005 Pharmaceutical Industry o Delivering needed therapeutics
More informationEveryday NMR. Innovation with Integrity. Why infer when you can be sure? NMR
Everyday NMR Why infer when you can be sure? Innovation with Integrity NMR Only NMR gives you definitive answers, on your terms. Over the past half-century, scientists have used nuclear magnetic resonance
More informationHigh Pressure Chemistry. Hydrogenation & Catalysis Tools.
High Pressure Chemistry Hydrogenation & Catalysis Tools www.helgroup.com HYDROGENATION AND CATALYSIS Product Selection Guide HEL Group s top quality high pressure reactors and systems offer innovative,
More informationPharma and Suppliers: Collaborating on Green Chemistry. Launch of PMI tool. ACS Green Chemistry Institute Pharmaceutical Roundtable
Pharma and Suppliers: Collaborating on Green Chemistry. Launch of PMI tool ACS Green Chemistry Institute Pharmaceutical Roundtable Dave Hughes 08-Feb-2011 2011 Copyright American Chemical Society Green
More informationReprinted from February Hydrocarbon
February2012 When speed matters Loek van Eijck, Yokogawa, The Netherlands, questions whether rapid analysis of gases and liquids can be better achieved through use of a gas chromatograph or near infrared
More informationMonitoring Emulsion Polymerization by Raman Spectroscopy
An Executive Summary Monitoring Emulsion Polymerization by Raman Spectroscopy Why process analytical matters to process development R&D. Serena Stephenson, PhD Senior R&D Analytical Manager Kishori Deshpande,
More information10.37 Exam 2 25 April, points. = 10 nm. The association rate constant
Problem 1: 35 points 10.37 Exam 2 25 April, 2007 100 points A protein and ligand bind reversibly with = 10 nm. The association rate constant k on = 2x10 4 M 1 s -1. The two species are mixed at an initial
More informationDevelopment of an organometallic flow chemistry. reaction at pilot plant scale for the manufacture of
Supporting Information Development of an organometallic flow chemistry reaction at pilot plant scale for the manufacture of verubecestat David A. Thaisrivongs*, John R. Naber*, Nicholas J. Rogus, and Glenn
More informationFocus Series Peptide Synthesizers
Focus Series Peptide Synthesizers aapptec is well known for its innovation and leadership in automated peptide synthesizers. aapptec technology has been an industry leader for the past 30 years around
More informationLecture (9) Reactor Sizing. Figure (1). Information needed to predict what a reactor can do.
Lecture (9) Reactor Sizing 1.Introduction Chemical kinetics is the study of chemical reaction rates and reaction mechanisms. The study of chemical reaction engineering (CRE) combines the study of chemical
More informationMadhav Sapre CTO Pi Process Intensification Mumbai
GREEN ENGINEERING & PROCESS OPTIMIZATION using Process Intensification Platforms Madhav Sapre CTO Pi Process Intensification Mumbai 22-04-2014 Copyright Pi-Process Intensification Experts LLP 1 Sustainable
More informationElectrolysis System CHLORINSITU V (PLUS)
Output of 100 3.500 g/h of ultra-pure active chlorine (hypochlorous acid) Electrolysis systems of the type CHLORINSITU V generate ultrapure active chlorine using the unique vacuum method with the membrane
More informationIs microwave chemistry scalable?
Is microwave chemistry scalable? Dr. Marilena Radoiu Microwave Technologies Consulting mradoiu@microwavetechs.com 1/16 Is microwave chemistry scalable? https://www.canstockphoto.com.au/illustration/ 2/16
More informationGo With the Flow Microfluidics and Microreactors: An Organic Chemist s New Round-Bottomed Flask
Go With the Flow Microfluidics and Microreactors: An Organic Chemist s New Round-Bottomed Flask Russell C. Smith Denmark Research Group Meeting 5/13/2008 Outline Introduction Design of Microreactors Methods
More informationCalorimetry Guide. Safety by Design What do we Learn from Reaction Calorimetry?
Calorimetry Guide What do we Learn from Reaction Calorimetry? Developing new compounds and transferring them to manufacturing requires an understanding of the chemical route, process and all its parameters.
More informationDr. OligoTM DNA / RNA / OLIGO SYNTHESIZERS
Dr. OligoTM DNA / RNA / OLIGO SYNTHESIZERS High Throughput Oligo Synthesis Synthesize Cleave Deprotect Desalt Elute Dr. Oligo TM The Dr. Oligo TM High Throughput Oligo Synthesizer is available in four
More informationNo. 6. Reaction Rate Constant in CSTR Reaction. 1. Introduction
No. 6. Reaction Rate Constant in CSTR Reaction 1. Introduction In the majority of industrial chemical processes, the reactor vessel in which the process takes place is the key item of equipment. The design
More informationMy Career in the Pharmaceutical Industry
SCI Career Options Seminar My Career in the Pharmaceutical Industry Simon Yates, AstraZeneca University of Sheffield 27 th November 2013 1998-2002 - Degree MChem. Undergraduate at University of York Final
More informationMICROWAVE CHEMISTRY OUT OF THE LAB AND INTO PRODUCTION
SYMPSIUM SERIES N. 157 EPIC 211 # 211 IChemE MICRWAVE CHEMISTRY UT F THE LAB AND INT PRDUCTIN Yvonne Wharton C-Tech Innovation Ltd, Capenhurst Technology Park, Capenhurst, Chester, CHI 6EH, UK; email:
More informationCoflore Agitated Cell Reactor
Coflore Agitated Cell Reactor Coflore ACR The Coflore ACR is a lab flow reactor developed by AM Technology for studying chemistry in flow and developing scalable continuous processes. Its flexible design
More informationSupporting Information. Adventures in Atropisomerism: Development of a Robust, Diastereoselective, Lithium-Catalyzed Atropisomer-Forming API Step
Supporting Information Adventures in Atropisomerism: Development of a Robust, Diastereoselective, Lithium-Catalyzed Atropisomer-Forming API Step Steven R. Wisniewski,* Ronald Carrasquillo-Flores, Federico
More informationSS. Trinità Hospital. Borgomanero, Italy. Dr. Anna Tinivella, Director of Diagnostics Department
SS. Trinità Hospital Borgomanero, Italy Dr. Anna Tinivella, Director of Diagnostics Department Consolidating laboratory services at three regional hospitals in Italy seemed like an almost impossible task,
More informationTHE FUTURE OF THE CHEMISTRY: CONTINUOUS FLOW REACTIONS BASEL 2016
THE FUTURE OF THE CHEMISTRY: CONTINUOUS FLOW REACTIONS BASEL 2016 CHEMICAL PLANT CONTINUOUS FLOW REACTOR The continuous flow reactor is a safe system, running chemical reactions in reduced volume with
More informationPRODUCTION OF URANOUS NITRATE WITH HYDRAZINE NITRATE AS REDUCING AGENT IN PRESENCE OF ADAMS CATALYST FOR URANIUM RECONVERSION PURPOSES
PRODUCTION OF URANOUS NITRATE WITH HYDRAZINE NITRATE AS REDUCING AGENT IN PRESENCE OF ADAMS CATALYST FOR URANIUM RECONVERSION PURPOSES Abstract: K.S. Rao, K Kumaraguru & P.M. Gandhi. Fuel Reprocessing
More informationThe integration of NeSSI with Continuous Flow Reactors and PAT for Process Optimization
The integration of NeSSI with Continuous Flow Reactors and PAT for Process Optimization Michael F. Roberto, Thomas I. Dearing and Brian J. Marquardt U.S. Food and Drug Administration 1 FDA Sponsored CFR
More informationParallel Kinetic Resolution. Group Meeting Timothy Chang
Parallel Kinetic Resolution (PKR) Group Meeting 09 29 2009 Timothy Chang Vedejs, E.; Chen, X. J. Am. Chem. Soc. 1997, 119, 2584. Tanaka, K.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 8078. KR versus PKR The
More informationSupporting Information
Supporting Information Continuous Flow Process for Reductive Deoxygenation of ω-chloroketone in the Synthesis of Vilazodone Avedis Karadeolian, Dineshkumar Patel, Prabhudas Bodhuri*, Gamini Weeratunga,
More informationOnline Reaction Monitoring of In-Process Manufacturing Samples by UPLC
Online Reaction Monitoring of In- Manufacturing Samples by UPLC Tanya Tollifson Waters Corporation, Milford, MA, USA APPLICATION BENEFITS Better throughput, yield, and process understanding are possible
More informationChiroSolve Enantiomer preparation for discovery, development and manufacturing
ChiroSolve Enantiomer preparation for discovery, development and manufacturing Presenter: Dr. Niteen A. Vaidya CTO, ChiroSolve Inc. 2065 Martin Ave. suite 107, Santa Clara, CA 95050 Telephone: (408) 834-8597
More informationHow to Safely Quantify a Reaction Exotherm
How to Safely Quantify a Reaction Exotherm One of the well publicised benefits of Flow Chemistry is the high available surface area and the superior heat transfer. This is particularly important with an
More informationAssessing Mixing Sensitivities for Scale-up. Matthew Jörgensen Atlanta, 10/20/2014
Assessing Mixing Sensitivities for Scale-up Matthew Jörgensen Atlanta, 10/20/2014 Nalas: Solutions that Scale! Engineering Services Broad range of services & capabilities supporting chemical process development
More informationApplication Note Pharmaceutical QA/QC. Agilent Application Solution. Authors. Abstract. Syed Salman Lateef Agilent Technologies, Inc.
Agilent Application Solution Transfer of a USP method for tolazamide from normal phase HPLC to SFC using the Agilent 126 Infinity Hybrid SFC/UHPLC System Improving peak shape and providing wider UV selectivity
More informationGreen Engineering using Commercial Flow Reaction & Process Intensification Platforms. Vijay Kirpalani. CEO Pi Process Intensification Mumbai
Green Engineering using Commercial Flow Reaction & Process Intensification Platforms Vijay Kirpalani CEO Pi Process Intensification Mumbai 08-12-2013 Copyright Pi-Process Intensification Experts LLP 1
More informationMethod Transfer between HPLC and UHPLC Instruments Equipment-related challenges and solutions
Method Transfer between HPLC and UHPLC Instruments Equipment-related challenges and solutions Today, ultra-high-performance liquid chromatography (UHPLC) has taken a firm foothold in the analytical laboratory.
More informationCHEMICAL REACTION ENGINEERING LAB
CHEMICAL REACTION ENGINEERING LAB EQUIPMENTS 1.CHEMICAL REACTORS SERVICE UNIT The chemical reactors service unit consists of a moulded ABS plinth which is used as a mounting for the chemical reactor to
More informationWhat is Flow Reactor. High efficiency reaction using Microreactor. Reaction example. Flow Reactor. What s Flow Reactor.
What s --------------------------- 176 KeyChem Series------------------------------- 177 Micro System ------------------- 177 Hydrogenation System------- 177 Flow Photoreactor System---------------------
More informationSIMATIC Ident Industrial Identification Systems
Related catalogs SIMATIC Ident Industrial Identification Systems Catalog ID 10 2012 Introduction System overview SIMATIC Ident 1 RFID systems for the HF frequency range SIMATIC RF200 SIMATIC RF300 MOBY
More informationIL H DESIGN FOR KRYPTON-85 ENRICHMENT BY THERMAL DIFFUSION
IL H DESIGN FOR KRYPTON-85 ENRICHMENT BY THERMAL DIFFUSION Roger A. Schwind and William M. Rutherford Monsanto Research Corporation Mound Laboratory* Miamisburg, Ohio 45342 Substantial quantities*of krypton
More informationION CHROMATOGRAPHY SYSTEM S 150
ION CHROMATOGRAPHY SYSTEM S 150 WATER ANALYSIS ENVIRONMENTAL ANALYSIS ANION & CATION ANALYSIS ION CHROMATOGRAPHY IIon Chromatography is an analytical separation technique based on ionic interactions. Dissolved
More informationData requirements for reactor selection. Professor John H Atherton
Data requirements for reactor selection Professor John H Atherton What is my best option for manufacturing scale? Microreactor Mesoscale tubular reactor Tubular reactor OBR (oscillatory baffled flow reactor)
More informationBATTERY MATERIALS SCALE-UP AND MANUFACTURING RESEARCH
rhtjhtyhy Getting Materials from Discovery to Production BATTERY MATERIALS SCALE-UP AND MANUFACTURING RESEARCH GREGRY KRUMDICK Materials Engineering Research Facility Program Manager International Battery
More informationProcess design decisions and project economics Dr. V. S. Moholkar Department of chemical engineering Indian Institute of Technology, Guwahati
Process design decisions and project economics Dr. V. S. Moholkar Department of chemical engineering Indian Institute of Technology, Guwahati Module - 02 Flowsheet Synthesis (Conceptual Design of a Chemical
More informationThe THT micro reaction calorimeter μrc
The THT micro reaction calorimeter μrc Titration calorimetry isothermal calorimetry and scanning calorimetry - all in one instrument CHEMICAL APPLICATIONS BROCHURE Introduction and reaction kinetics The
More information12 Moderator And Moderator System
12 Moderator And Moderator System 12.1 Introduction Nuclear fuel produces heat by fission. In the fission process, fissile atoms split after absorbing slow neutrons. This releases fast neutrons and generates
More information(CATION EXCHANGE AND LN RESIN, WITH VACUUM BOX SYSTEM)
Analytical Procedure RADIUM IN WATER (CATION EXCHANGE AND LN RESIN, WITH VACUUM BOX SYSTEM) 1. SCOPE 1.1. This is a method for separation and measurement of radium-226 and radium-228 in water. This method
More informationThe THT micro reaction calorimeter RC
The THT micro reaction calorimeter RC Titration calorimetry isothermal calorimetry and scanning calorimetry - all in one instrument C H E M I C A L A P P L I C A T I O N S B R O C H U R E Introduction
More informationAutomated Microdosing System for Integration With a Miniaturized High-pressure Reactor System
Journal of Automated Methods & Management in Chemistry, 5 (5), no., 3 3 c 5 Hindawi Publishing Corporation Automated Microdosing System for Integration With a Miniaturized High-pressure Reactor System
More informationCHAPTER 3 : MATHEMATICAL MODELLING PRINCIPLES
CHAPTER 3 : MATHEMATICAL MODELLING PRINCIPLES When I complete this chapter, I want to be able to do the following. Formulate dynamic models based on fundamental balances Solve simple first-order linear
More informationThe Development of an Integrated Control Strategy for a Continuous Primary Pharmaceutical Process
The Development of an Integrated Control Strategy for a Continuous Primary Pharmaceutical Process Hannah Robinson GlaxoSmithKine 2 nd International Symposium on Continuous Manufacturing of Pharmaceuticals,
More informationUsing Design of Experiments to Optimize Chiral Separation
1 of 7 10/5/2010 1:15 PM Home About us Guidance e-newsletter Expert Insights Readers' Choice Resources Audio & Video» QbD News Categorized Expert Insights, Resources Using Design of Experiments to Optimize
More informationThermo Scientific ICP-MS solutions for the semiconductor industry. Maximize wafer yields with ultralow elemental detection in chemicals and materials
Thermo Scientific ICP-MS solutions for the semiconductor industry Maximize wafer yields with ultralow elemental detection in chemicals and materials Trace impurity analysis in chemicals an used in the
More informationDevelopment of Safe and Scalable Continuous-Flow Methods for. Palladium-Catalyzed Aerobic Oxidation Reactions
Supplementary Data for Development of Safe and Scalable Continuous-Flow Methods for Palladium-Catalyzed Aerobic Oxidation Reactions Xuan Ye, a Martin D. Johnson, *b Tianning Diao, a Matthew H. Yates *b
More informationDevelopment and Implementation of Continuous Manufacturing Processes for API
Development and Implementation of Continuous Manufacturing Processes for API Paul C. Collins, Ph.D., Senior Director Small Molecule Design and Development Eli Lilly and Company Outline Introduction to
More informationNMR Solutions for drug discovery
NMR Solutions for drug discovery Dr. Matteo Pennestri London, UK Bruker Users Meeting Innovation with Integrity The principle of Fragment Based Screening from efficient fragments to Drug candidates Fragment
More informationThe Vacuum Sorption Solution
The Total Sorption Solution The Vacuum Sorption Solution The Vacuum Sorption Solution www.thesorptionsolution.com About the Technique DVS Vacuum - the only gravimetric system that supports static and dynamic
More informationTHE USE OF DEWAR CALORIMETRY IN THE ASSESSMENT OF CHEMICAL REACTION HAZARDS
THE USE OF DEWAR CALORIMETRY IN THE ASSESSMENT OF CHEMICAL REACTION HAZARDS R.L. ROGERS* Dewar Calorimetry is one of the simplest and most useful techniques used in the assessment of chemical reaction
More informationAdvanced Olefin Polymer Reactor Fundamentals and Troubleshooting
Page 1 of 6 Advanced Olefin Polymer Reactor Fundamentals and Troubleshooting Introduction The success of every company depends of each employee s understanding of the business s key components. Employee
More informationTHINK FLUID DYNAMIX Mixing, Homogenization & Blend Time. THINK Fluid Dynamix
THINK FLUID DYNAMIX Mixing, Homogenization & Blend Time Provided by: THINK Fluid Dynamix Am Pestalozziring 21 D-91058 Erlangen (Germany) Tel. +49 (0)9131 69098-00 http://www.think-fd.com CFD ENGINEERING
More informationRight. First Time in Fine-Chemical Process Scale-up. Lum(Bert)us A. Hulshof. Avoiding scale-up problems: the key to rapid success
Right First Time in Fine-Chemical Process Scale-up Avoiding scale-up problems: the key to rapid success Lum(Bert)us A. Hulshof Eindhoven University of Technology Eindhoven, The Netherlands V Preface About
More informationA Quality by Design (QbD) Based Method Development for the Determination of Impurities in a Peroxide Degraded Sample of Ziprasidone
A Quality by Design (QbD) Based Method Development for the Determination of Impurities in a Peroxide Degraded Sample of Ziprasidone Mia Summers and Kenneth J. Fountain Waters Corporation, 34 Maple St.,
More informationAspen Polymers. Conceptual design and optimization of polymerization processes
Aspen Polymers Conceptual design and optimization of polymerization processes Aspen Polymers accelerates new product innovation and enables increased operational productivity for bulk and specialty polymer
More informationBAE 820 Physical Principles of Environmental Systems
BAE 820 Physical Principles of Environmental Systems Acquisition of reaction rate data Dr. Zifei Liu Uncertainties in real world reaction rate data Most interesting reaction systems involves multiple reactions,
More informationFinex. Tailor-Made Ion Exchange Resins for Water Treatment Tiia Aromaa, 2012
Finex Tailor-Made Ion Exchange Resins for Water Treatment Tiia Aromaa, tiia.aromaa@finex.fi 2012 Finex in a nutshell Location: History: Kotka, Finland - Resin production at current location in Kotka was
More informationThermodynamics and the Solubility of Sodium Tetraborate Decahydrate
Thermodynamics and the Solubility of Sodium Tetraborate Decahydrate In this experiment you, as a class, will determine the solubility of sodium tetraborate decahydrate (Na 2 B 4 O 7 10 H 2 O or Na 2 [B
More informationInsightXpress 12 Sep Anna Codina, Product Portfolio Manager, Pharma Market, BBIO// Matteo Pennestri, PM InsightXpress, BBIO
Insight 12 Sep 2017 Anna Codina, Product Portfolio Manager, Pharma Market, BBIO// Matteo Pennestri, PM Insight, BBIO How Fast is Fast? Transfer times in the order of minutes Mixing Acquisition Standard
More informationExperiment 9: Synthesis and Isolation of Optical Isomers of a Cobalt (III) Compound CH3500: Inorganic Chemistry, Plymouth State University
Experiment 9: Synthesis and Isolation of Optical Isomers of a Cobalt (III) Compound CH3500: Inorganic Chemistry, Plymouth State University Adapted from GS Girolami, TB Rauchfuss, RJ Angelici, "Experiment
More informationTheoretical Models of Chemical Processes
Theoretical Models of Chemical Processes Dr. M. A. A. Shoukat Choudhury 1 Rationale for Dynamic Models 1. Improve understanding of the process 2. Train Plant operating personnel 3. Develop control strategy
More information3D-Printed Metal Flow Reactors and Mixers
3D-Printed Metal Flow Reactors and Mixers RSC Symposium 2017 Chemspec, Muenchen Germany May 31 June 1, 2017 André de Vries www.innosyn.com Development of Micro/Flow Reactor Five key phases (Gartner) Limited
More informationBIOO FOOD AND FEED SAFETY. Histamine Enzymatic Assay Kit Manual. Catalog #: Reference #:
BIOO FOOD AND FEED SAFETY Histamine Enzymatic Assay Kit Manual Catalog #: 1032-05 Reference #: 1032-05 BIOO Scientific Corp. 2010 TABLE OF CONTENTS GENERAL INFORMATION... 1 Product Description... 1 Procedure
More informationServices in Chemistry for a Sustainable World
Table of Content 2 Services in Chemistry for a Sustainable World COMPANY PROFILE TECHNICAL PROFILE General Information... 3 Our Services... 4 Project Types & Pricing Options... 5 Reaction & Catalyst Portfolio...
More informationProduct Information. Silicon Carbide Well Plates
Silicon Carbide Well Plates Silicon carbide (SiC) is the perfect material to ensure temperature homogeneity in rectangular multiwell reactors in a microwave field. The high microwave absorbance and excellent
More informationMultiVap8: Automated concentration system
MultiVap8: Automated concentration system Introduction Solvent evaporation is an essential step of sample preparation before chromatographic analysis and is commonly used in a variety of applications including
More informationInvestigation of Petasis and Ugi Reactions in Series in an Automated Microreactor System
Electronic Supplementary Material (ESI) for RSC Advances. This journal is The Royal Society of Chemistry 2014 Supplementary Information Investigation of Petasis and Ugi Reactions in Series in an Automated
More informationTo use calorimetry results to calculate the specific heat of an unknown metal. To determine heat of reaction ( H) from calorimetry measurements.
Calorimetry PURPOSE To determine if a Styrofoam cup calorimeter provides adequate insulation for heat transfer measurements, to identify an unknown metal by means of its heat capacity and to determine
More informationFormation of valine microcrystals through rapid antisolvent precipitation
Formation of valine microcrystals through rapid antisolvent precipitation Miroslav Variny a, Sandra Alvarez de Miguel b, Barry D. Moore c, Jan Sefcik b a Department of Chemical and Biochemical Engineering,
More informationFlowCAT a versatile continuous flow reactor system focusing on reactions under elevated pressure and/or involving heterogeneous catalysis.
1 FlowCAT - a versatile continuous flow reactor system FlowCAT a versatile continuous flow reactor system focusing on reactions under elevated pressure and/or involving heterogeneous catalysis. By Dr Jasbir
More information