Continuous-Flow Synthesis and Purification of Atropine with Sequential In-Line Separations of Structurally Similar Impurities

被引：40

作者：

Dai, Chunhui ^{[1
]}

Snead, David R. ^{[1
]}

Zhang, Ping ^{[1
]}

Jamison, Timothy F. ^{[1
]}

机构：

[1] MIT, Dept Chem, Cambridge, MA 02139 USA

来源：

JOURNAL OF FLOW CHEMISTRY | 2015年 / 5卷 / 03期

关键词：

continuous-flow synthesis; membrane separation; atropine; TROPANE ALKALOIDS; MULTISTEP SYNTHESIS; CHEMISTRY; IBUPROFEN; SYSTEMS;

D O I：

10.1556/1846.2015.00013

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Flow chemistry has attracted significant interest in pharmaceutical development, where substantial efforts have been directed toward the design of continuous processes. Here, we report a total synthesis of atropine in flow that features an unusual hydroxymethylation and separation of several by products with high structural similarity to atropine. Using a combination of careful pH control in three sequential liquid-liquid extractions and a functionalized resin, atropine is delivered by the flow system with >98% purity.

引用

收藏

页码：133 / 138

页数：6

相关论文

共 43 条

[1] Membrane-Based, Liquid-Liquid Separator with Integrated Pressure Control [J].

Adamo, Andrea ;

Heider, Patrick L. ;

Weeranoppanant, Nopphon ;

Jensen, Klavs F. .

INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH, 2013, 52 (31) :10802-10808

[2] Using Continuous Processes to Increase Production [J].

Anderson, Neal G. .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2012, 16 (05) :852-869

[3] A Machine-Assisted Flow Synthesis of SR48692: A Probe for the Investigation of Neurotensin Receptor-1 [J].

Battilocchio, Claudio ;

Deadman, Benjamin J. ;

Nikbin, Nikzad ;

Kitching, Matthew O. ;

Baxendale, Ian R. ;

Ley, Steven V. .

CHEMISTRY-A EUROPEAN JOURNAL, 2013, 19 (24) :7917-7930

[4] The Continuous-Flow Synthesis of Ibuprofen [J].

Bogdan, Andrew R. ;

Poe, Sarah L. ;

Kubis, Daniel C. ;

Broadwater, Steven J. ;

McQuade, D. Tyler .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2009, 48 (45) :8547-8550

[5] One-pot oxidative N-demethylation of tropane alkaloids with hydrogen peroxide and a FeIII-TAML catalyst [J].

Do Pham, Duy D. ;

Kelso, Geoffrey F. ;

Yang, Yuanzhong ;

Hearn, Milton T. W. .

GREEN CHEMISTRY, 2012, 14 (04) :1189-1195

[6]

Gadzikowska Maria, 2002, Acta Pol Pharm, V59, P149

[7] Chemical Assembly Systems: Layered Control for Divergent, Continuous, Multistep Syntheses of Active Pharmaceutical Ingredients [J].

Ghislieri, Diego ;

Gilmore, Kerry ;

Seeberger, Peter H. .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2015, 54 (02) :678-682

[8]

Gore V, 2014, US Patent, Patent No. [2014/102829 Al, 2014102829]

[9]

Grynkiewicz G, 2008, PHARMACOL REP, V60, P439

[10] Continuous metal scavenging and coupling to one-pot copper-catalyzed azide-alkyne cycloaddition click reaction in flow [J].

Gursel, Iris Vural ;

Aldiansyah, Ferry ;

Wang, Qi ;

Noel, Timothy ;

Hessel, Volker .

CHEMICAL ENGINEERING JOURNAL, 2015, 270 :468-475

← 1 2 3 4 5 →