Jamison, T. F. et al.: 2018 Science of Synthesis, 2018/5: Flow Chemistry in Organic Synthesis DOI: 10.1055/sos-SD-228-00268
Flow Chemistry in Organic Synthesis

15.2 Flow Chemistry in the Pharmaceutical Industry: Part 2

More Information

Book

Editors: Jamison, T. F.; Koch, G.

Authors: Beeler, A. B.; Beingessner, R. L.; Bottecchia, C.; Browne, D. L.; Coley, C. W.; Ferguson, S.; Folgueiras-Amador, A. A.; Gilmore, K.; Hicklin, R. W.; Imbrogno, J.; Itsuno, S.; Jamison, T. F.; Jensen, K. F.; Kelly, L. P.; Kerr, M. S.; Kiesman, W. F.; Kim, H.; Kwok, D.-I. A.; Ley, S. V.; Longstreet, A. R.; May, S. A. ; McTeague, T. A.; Mijalis, A. J.; Mo, Y.; Moon, S.; Myerson, A.; Noël, T.; O’Brien, A. G.; O’Brien, M.; O’Mahony, M.; Opalka, S. M.; Pentelute, B. L.; Polyzos, A. ; Schepartz, A.; Seeberger, P. H.; Seo, H.; Steinauer, A.; Stelzer, T.; Stephenson, C. R. J.; Strom, A. E.; Styduhar, E. D.; Sun, A. C.; Telmesani, R.; Thomas, D. A.; Tran, T. H.; Ullah, M. S.; Wicker, A. C.; Wirth, T.; Yoshida, J.

Title: Flow Chemistry in Organic Synthesis

Print ISBN: 9783132423312; Online ISBN: 9783132423350; Book DOI: 10.1055/b-006-161272

Subjects: Organic Chemistry;Chemical Reactions, Catalysis;Organometallic Chemistry;Laboratory Techniques, Stoichiometry

Science of Synthesis Reference Libraries



Parent publication

Title: Science of Synthesis

DOI: 10.1055/b-00000101

Series Editors: Fürstner (Editor-in-Chief), A.; Carreira, E. M.; Faul, M.; Kobayashi, S.; Koch, G.; Molander, G. A.; Nevado, C.; Trost, B. M.; You, S.-L.

Type: Multivolume Edition

 


Abstract

The development and application of continuous-flow drug-substance manufacturing at Eli Lilly is described. A series of examples are provided in which a continuous process was developed to solve problems associated with an existing batch process. The three distinct areas of focus are: facilitation of early phase delivery, hybrid batch/flow processes at manufacturing scale, and small-volume continuous manufacturing (linked multiunit operation processes at 10 kg/day throughput). An overview is provided of the types of reactors implemented in our program and the chemistries they enable. The use of online process analytical technology is also described for each of these systems. Special emphasis is placed on the examples pertaining to increased safety and improved product quality gained from flow processing.

 
  • 1 Gutmann B, Cantillo D, Kappe CO. Angew. Chem. Int. Ed 2015; 54: 6688
  • 2 Lee SL, OʼConnor TF, Yang X, Cruz CN, Chatterjee S, Madurawe RD, Moore CMV, Yu LX, Woodcock J. J. Pharm. Innov 2015; 10: 191
  • 3 Proceeding: FDA-AIChE Workshop on Adopting Continuous Manufacturing, 29 Feb. 2016, Collins, P. C., Ed.; www.aiche.org/conferences/fda-aiche-workshop-on-adopting-continuous-manufacturing/2016/proceeding/group/general-program (accessed August 2018).
  • 4 Fischer E. Going with the flow: continuous manufacturing.
  • 5 Challener C. GlaxoSmithKline Adopts Continuous Manufacturing for Preparation of Key Intermediate.
  • 6 Rincón JA, Barberis M, González-Esguevillas M, Johnson MD, Niemeier JK, Sun W.-M. Org. Process Res. Dev 2011; 15: 1428
  • 7 May SA, Johnson MD, Braden TM, Calvin JR, Haeberle BD, Jines AR, Miller RD, Plocharczyk EF, Rener GA, Richey RN, Schmid CR, Vaid RK, Yu H. Org. Process Res. Dev 2012; 16: 982
  • 8 White TD, Alt CA, Cole KP, McClary Groh J, Johnson MD, Miller RD. Org. Process Res. Dev 2014; 18: 1482
  • 9 Cole KP, Campbell BM, Forst MB, McClary Groh J, Hess M, Johnson MD, Miller RD, Mitchell D, Polster CS, Reizman BJ, Rosemeyer M. Org. Process Res. Dev 2016; 20: 820
  • 10 Tsukanov SV, Johnson MD, May SA, Rosemeyer M, Watkins MA, Kolis SP, Yates MH, Johnston JN. Org. Process Res. Dev 2016; 20: 215
  • 11 Slattery CN, Deasy RE, Maguire AR, Kopach ME, Singh UK, Argentine MD, Trankle WG, Scherer RB, Moynihan H. J. Org. Chem 2013; 78: 5955
  • 12 Kopach ME, Cole KP, Pollock PM, Johnson MD, Braden TM, Webster LP, McClary Groh J, McFarland AD, Schafer JP, Adler JJ, Rosemeyer M. Org. Process Res. Dev 2016; 20: 1581
  • 13 Osterberg PM, Niemeier JK, Welch CJ, Hawkins JM, Martinelli JR, Johnson TE, Root TW, Stahl SS. Org. Process Res. Dev 2015; 19: 1537
  • 14 May SA, Johnson MD, Buser JY, Campbell AN, Frank SA, Haeberle BD, Hoffman PC, Lambertus GR, McFarland AD, Moher ED, White TD, Hurley DD, Corrigan AP, Gowran O, Kerrigan NG, Kissane MG, Lynch RR, Sheehan P, Spencer RD, Pulley SR, Stout JR. Org. Process Res. Dev 2016; 20: 1870
  • 15 Johnson MD, May SA, Haeberle B, Lambertus GR, Pulley SR, Stout JR. Org. Process Res. Dev 2016; 20: 1305
  • 16 Johnson MD, May SA, Calvin JR, Lambertus GR, Kokitkar PB, Landis CR, Jones BR, Abrams ML, Stout JR. Org. Process Res. Dev 2016; 20: 888
  • 17 Chen X, Frank SA, Remick DM, Pedersen SW. US 2010 331 309, 2010
  • 18 Frederick MO, Frank SA, Vicenzi JT, LeTourneau ME, Berglund KD, Edward AW, Alt CA. Org. Process Res. Dev 2014; 18: 546
  • 19 Cole KP, Ryan SJ, McClary Groh J, Miller RD. Bioorg. Med. Chem 2017; 25: 6209
  • 20 Frederick MO, Calvin JR, Cope RF, LeTourneau ME, Lorenz KT, Johnson MD, Maloney TD, Pu YJ, Miller RD, Cziesla LE. Org. Process Res. Dev 2015; 19: 1411
  • 21 Eli Lilly to invest €35m in Kinsale plant, 5 April 2016; www.irishtimes.com/business/health-pharma/eli-lilly-to-invest-35m-in-kinsale-plant-1.2598781 (accessed August 2018).
  • 22 White TD, Berglund KD, McClary Groh J, Johnson MD, Miller RD, Yates MH. Org. Process Res. Dev 2012; 16: 939
  • 23 Johnson MD, May SA, Calvin JR, Remacle J, Stout JR, Diseroad WD, Zaborenko N, Haeberle BD, Sun W.-M, Miller MT, Brennan J. Org. Process Res. Dev 2012; 16: 1017
  • 24 Cole KP, McClary Groh J, Johnson MD, Burcham CL, Campbell BM, Diseroad WD, Heller MR, Howell JR, Kallman NJ, Koenig TM, May SA, Miller RD, Mitchell D, Myers DP, Myers SS, Phillips JL, Polster CS, White TD, Cashman J, Hurley D, Moylan R, Sheehan P, Spencer RD, Desmond K, Desmond P, Gowran O. Science (Washington, D. C.) 2017; 356: 1144