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Preparation, Characterization and Crystal Structures of a Key Intermediate, and a Significant Impurity, in the Synthesis of Repaglinide

  • Gui-Mei Tang
  • Yong-Tao WangEmail author
  • Yu-Song Wu
Original Paper

Abstract

The crystal structure of 2-(3-ethoxy-4-(methoxycarbonyl)phenyl) acetic acid (RGA), an important intermediate in the preparation of Repaglinide, has been carried out. Hydrogen bonds between the carboxylate groups link the molecules into dimers while weak C–H···π interactions link these dimers into a one-dimensional chain lying along the crystallographic b axis. 4-(Carboxymethyl)-2-ethoxybenzoic acid (RGAA), an impurity observed in the preparation of Repaglinide, has been simply synthesized by the hydrolysis of RGA under basic conditions. Hydrogen bonds between the carboxylate groups link the molecules into dimers while weak C–H···O interactions connect these dimers into a one-dimensional chain lying along the crystallographic c axis. The compound RGAA has also been characterized by FT-IR and UV–Vis spectra, and by 1H NMR analysis. RGA: monoclinic, P21/n, a = 12.848(3) Å, b = 4.5539(10) Å, c = 22.328(5) Å, α = 90°, β = 101.703(5)°, γ = 90°, V = 1279.2(5) Å3. RGAA: monoclinic, P21/n, a = 14.0877(11) Å, b = 5.1814(3) Å, c = 14.5857(11) Å, α = 90°, β = 91.578(3)°, γ = 90°, V = 1064.26(13) Å3. The thermal behaviors and fluorescence properties of RGAA were also investigated.

Graphic Abstract

The crystal structures of one key intermediate of Repaglinide and its derivative have been characterized, where their luminescence properties and thermal behavior have been investigated.

Keywords

Repaglinide Intermediate Infrared spectra UV–Vis and NMR spectra X-ray diffraction Crystal structures Thermal behavior Photoluminescence 

Notes

Acknowledgements

This work was financially supported by the Project of Shandong Province Higher Educational Science and Technology Program (J09LB03), Shandong Distinguished Middle-aged Young Scientist Encouragement and Reward Foundation (BS2011CL034), and Shandong Province Natural Scientific Foundation (ZR2017MB041). We thanks to one of reviewers giving a lot of good comments.

Supplementary material

10870_2019_811_MOESM1_ESM.docx (286 kb)
Supplementary material 1 (DOCX 286 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Chemical EngineeringQilu University of Technology (Shandong Academy of Sciences)JinanChina

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