--- title: "Amide coupling: EDC/HOBt Template – Chemistry Diagram | MolDraw" url: https://www.moldraw.com/templates/research-peptide-coupling/ description: "Amide coupling: EDC/HOBt template: EDC activates the acid as an O-acylisourea; HOBt intercepts it as the OBt ester, which the amine attacks to give the amide…" lang: en publisher: Scidart Academy generated: 2026-10-28 --- [MolDraw](https://www.moldraw.com/) › [Templates](https://www.moldraw.com/templates/) › [Research figures](https://www.moldraw.com/templates/research-figures/) › Amide coupling: EDC/HOBt [Research figures](https://www.moldraw.com/templates/research-figures/)Premium # Amide coupling: EDC/HOBt template ![Amide coupling: EDC/HOBt template: EDC activates the acid as an O-acylisourea; HOBt intercepts it as the OBt ester, which the amine attacks to give the amide and the water-soluble urea. Key points cover HATU, racemisation and N-acylurea.](https://www.moldraw.com/templates/research-peptide-coupling.webp) [Edit in MolDraw](https://www.moldraw.com/)Download with Pro Premium template. Preview and edit it free in MolDraw; downloading and exporting it is part of [MolDraw Pro](https://www.moldraw.com/pricing). EDC activates the acid as an O-acylisourea; HOBt intercepts it as the OBt ester, which the amine attacks to give the amide and the water-soluble urea. Key points cover HATU, racemisation and N-acylurea. ## Mechanism step by step Carbodiimide activation: O-acylisourea, then the OBt active ester, then the amide 1. **Proton transfer** – The acid protonates the carbodiimide N 2. **O-Acylisourea** – Carboxylate adds to the central carbon 3. **OBt active ester** – OBt⁻ takes the acyl group; the isourea leaves (it becomes the urea) 4. **Aminolysis** – The amine takes the acyl group; OBt⁻ (HOBt) is released 5. **Deprotonation** – Base (or OBt⁻) gives the neutral amide ## Key points - EDC (R³ = Et, R⁴ = (CH₂)₃NMe₂) gives a water-soluble urea, washed out in the work-up; DCC gives insoluble DCU, removed by filtration. - Without HOBt the O-acylisourea can rearrange (O→N acyl shift) to an unreactive N-acylurea, or cyclise to an oxazolone that racemises α-stereocentres. - HATU (a HOAt-derived aminium salt) with iPr₂NEt forms the OAt ester directly: faster, with less epimerisation (neighbouring pyridine N). - Steps 3 and 4 are drawn as one-step acyl transfers for clarity; each goes through a tetrahedral intermediate (addition, then loss of the leaving group). - Anhydrous HOBt is an explosive hazard; it is sold wetted. Usual order: acid + EDC/HOBt first, then the amine. Drawn with 159 atoms, 16 arrows, 7 shapes – every one editable in MolDraw. ## Sources - [Montalbetti & Falque, Tetrahedron 2005, 61, 10827](https://doi.org/10.1016/j.tet.2005.08.031) Review - [Valeur & Bradley, Chem. Soc. Rev. 2009, 38, 606](https://doi.org/10.1039/b701677h) Review - [Carpino, J. Am. Chem. Soc. 1993, 115, 4397](https://doi.org/10.1021/ja00063a082) Original paper - [Clayden, Greeves & Warren, Organic Chemistry, 2nd ed., OUP 2012](https://openlibrary.org/isbn/9780199270293) Textbook ## How to use this template 1. Press **Edit in MolDraw**. The template opens on the canvas of the free MolDraw editor. 2. Change anything: move structures, edit atoms and labels, recolour highlights or delete what you do not need. 3. Add your own structures, arrows and text next to it, or combine several templates on one page. 4. Export the drawing as PNG, SVG or PDF for slides, worksheets, theses and papers. ## Frequently asked questions ### Is the Amide coupling: EDC/HOBt template free? You can preview the Amide coupling: EDC/HOBt template here and open and edit it in MolDraw for free. Downloading or exporting it is part of MolDraw Pro, together with the other premium templates. ### Can I edit the Amide coupling: EDC/HOBt template? Yes. It opens as an ordinary MolDraw drawing, so every structure, arrow, label and colour can be changed, and you can add your own content around it. ### Is the chemistry checked? Every structure is checked with RDKit and every curly arrow passes MolDraw’s electron-flow audit. The sources used are listed on this page. ### Are the research figure templates suitable for journals? They follow common ACS and RSC figure conventions (scheme layout, numbered compounds, condition text above and below arrows). 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