Synthesis of Urea Derivatives in Two Sequential Continuous-Flow Reactors

A continuous-flow system consisting of two sequential microreactors was developed for the synthesis of nonsymmetrically substituted ureas starting from tert-butoxycarbonyl protected amines. Short reaction times could be achieved under mild conditions. In-line FT-IR analytical technique was used to m...

Full description

Saved in:
Bibliographic Details
Published inOrganic process research & development Vol. 21; no. 4; pp. 611 - 622
Main Authors Bana, Péter, Lakó, Ágnes, Kiss, Nóra Zsuzsa, Béni, Zoltán, Szigetvári, Áron, Kóti, János, Túrós, György István, Éles, János, Greiner, István
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 21.04.2017
Amer Chemical Soc
Subjects
Chemistry
Chemistry, Applied
Chemistry, Organic
Physical Sciences
Science & Technology
ORGANIC-SYNTHESIS
BOC-PROTECTED AMINES
ONE-POT SYNTHESIS
DIMETHYLSULFOXIDE
CHEMISTRY
ONLINE IR ANALYSIS
UNSYMMETRICAL UREAS
DISSOCIATION-CONSTANTS
ACTIVE PHARMACEUTICAL INGREDIENTS
MULTISTEP SYNTHESIS
Online AccessGet full text

Cover

More Information
Summary:A continuous-flow system consisting of two sequential microreactors was developed for the synthesis of nonsymmetrically substituted ureas starting from tert-butoxycarbonyl protected amines. Short reaction times could be achieved under mild conditions. In-line FT-IR analytical technique was used to monitor the reaction, including the formation of the isocyanate intermediate, thus allowing optimization of the reagent ratios. The mechanistic role of the applied base was also clarified. The setup was successfully utilized for the synthesis of several urea derivatives including the active pharmaceutical ingredient cariprazine.
ISSN:1083-6160
1520-586X
DOI:10.1021/acs.oprd.7b00019