Scale-Up of a Continuous Extraction Process for Driving an Equilibrium-Limited Reaction to Completion

被引:5
作者
Tudesco, Michael T. [1 ]
Moschetta, Eric G. [1 ]
Voight, Eric A. [2 ]
机构
[1] AbbVie Inc, Proc Res & Dev, 1401 Sheridan Rd, N Chicago, IL 60064 USA
[2] AbbVie Inc, Discovery Chem & Technol, 1 North Waukegan Rd, N Chicago, IL 60064 USA
关键词
continuous extraction; equilibrium reaction; deprotection; scale-up; LIQUID-LIQUID-EXTRACTION; WORK-UP; SEPARATION; OXIDATION; CATALYST; DESIGN;
D O I
10.1021/acs.oprd.8b00260
中图分类号
O69 [应用化学];
学科分类号
081704 ;
摘要
We report a strategy for implementing a scalable continuous extraction to drive an equilibrium limited reaction to completion. Our approach is simple, requiring only standard equipment and glassware, and can be designed to meet the needs of the process (e.g., reduced cycle time or reduced solvent use) with minimal development time. We investigated the process parameters, such as the flow rate of fresh n-heptane (extracting solvent) into the system, at a 0.5-5 g scale and reduced the overall time and total amount of n-heptane needed to drive the reaction to completion. The improved conditions for the extraction were demonstrated at the SO g scale, leading to a similar yield of the desired product and total reaction time as at the 5 g scale, verifying that our reactions and extraction conditions were scalable. In particular, our fit-for-purpose approach is customizable to a number of systems and can be implemented in a short period of time with a limited amount of material.
引用
收藏
页码:1564 / 1569
页数:6
相关论文
共 23 条
[11]   A Continuous-Flow Approach to 3,3,3-Trifluoromethylpropenes: Bringing Together Grignard Addition, Peterson Elimination, Inline Extraction, and Solvent Switching [J].
Hamlin, Trevor A. ;
Lazarus, Gillian M. L. ;
Kelly, Christopher B. ;
Leadbeater, Nicholas E. .
ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2014, 18 (10) :1253-1258
[12]   Development of a Multi-Step Synthesis and Workup Sequence for an Integrated, Continuous Manufacturing Process of a Pharmaceutical [J].
Heider, Patrick L. ;
Born, Stephen C. ;
Basak, Soubir ;
Benyahia, Brahim ;
Lakerveld, Richard ;
Zhang, Haitao ;
Hogan, Rachael ;
Buchbinder, Louis ;
Wolfe, Aaron ;
Mascia, Salvatore ;
Evans, James M. B. ;
Jamison, Timothy F. ;
Jensen, Klavs F. .
ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2014, 18 (03) :402-409
[13]   Model-Based Solvent Selection during Conceptual Process Design of a New Drug Manufacturing Process [J].
Hsieh, Daniel ;
Marchut, Alexander J. ;
Wei, Chenkou ;
Zheng, Bin ;
Wang, Steve S. Y. ;
Kiang, San .
ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2009, 13 (04) :690-697
[14]   Development and Scale-Up of a Continuous, High-Pressure, Asymmetric Hydrogenation Reaction, Workup, and Isolation [J].
Johnson, Martin D. ;
May, Scott A. ;
Calvin, Joel R. ;
Remacle, Jacob ;
Stout, James R. ;
Diseroad, William D. ;
Zaborenko, Nikolay ;
Haeberle, Brian D. ;
Sun, Wei-Ming ;
Miller, Michael T. ;
Brennan, John .
ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2012, 16 (05) :1017-1038
[15]   Biphasic Catalytic Hydrogen Peroxide Oxidation of Alcohols in Flow: Scale-up and Extraction [J].
Peer, Maryam ;
Weeranoppanant, Nopphon ;
Adamo, Andrea ;
Zhang, Yanjie ;
Jensen, Klays F. .
ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2016, 20 (09) :1677-1685
[16]   Continuous chiral separation of amino acid derivatives by enantioselective liquid-liquid extraction in centrifugal contactor separators [J].
Schuur, Boelo ;
Floure, Joelle ;
Hallett, Andrew J. ;
Winkelman, Jozef G. M. ;
de Vries, Johannes G. ;
Heeres, Hero J. .
ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2008, 12 (05) :950-955
[17]   Scalable Enantioseparation of Amino Acid Derivatives Using Continuous Liquid-Liquid Extraction in a Cascade of Centrifugal Contactor Separators [J].
Schuur, Boelo ;
Hallet, Andrew J. ;
Winkelman, Jozef G. M. ;
de Vries, Johannes G. ;
Heeres, Hero J. .
ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2009, 13 (05) :911-914
[18]   High-Throughput Extractions: A New Paradigm for Workup Optimization in Pharmaceutical Process Development [J].
Selekman, Joshua A. ;
Tran, Kristy ;
Xu, Zhongmin ;
Dummeldinger, Michael ;
Kiau, Susanne ;
Nolfo, Joseph ;
Janey, Jacob .
ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2016, 20 (10) :1728-1737
[19]   Proof of concept for continuous enantioselective liquid-liquid extraction in capillary microreactors using 1-octanol as a sustainable solvent [J].
Susanti ;
Meinds, Tim G. ;
Pinxterhuis, Erik B. ;
Schuur, Boelo ;
de Vries, Johannes G. ;
Feringa, Ben L. ;
Winkelman, Jozef G. M. ;
Yue, Jun ;
Heeres, Hero J. .
GREEN CHEMISTRY, 2017, 19 (18) :4334-4343
[20]   Sustainability Improvements through Catalyst Recycling in a Liquid-Liquid Batch and Continuous Phase Transfer Catalyzed Process [J].
Teoh, Soo Khean ;
Toh, Qiao Yan ;
Noorulameen, Mohammad Salih ;
Sharratt, Paul N. .
ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2017, 21 (04) :520-530