TCFH – a safe, affordable reagent for ester and difficult amide synthesis
CAS: 207915-99-9, 94790-35-9
Synonym: Chloro-N,N,N′,N′-tetramethylformamidinium hexafluorophosphate
Properties
Purity
≥98.0%
Molecular Formula
C5H12ClF6N2P
Molecular Weight
280.58 [gr/mol]
Appearance
White to off-white crystalline powder
Storage Conditions
Store in a cool and dry place (2-8oC)
Applications
TCFH, as a reagent, has several advantages besides being economical:
- Due to its high coupling potency, it might be used in reactions previously only accomplished using carbodiimide-mediated couplings, extending in this manner its application for the formation of esters, diacyl amides, and acylation of non-reactive amines
- It is a solid, reasonably stable compound when stored around 0°C
- Using widely available coupling additives, the chemist can determine an optimal reagent ratio to balance product yield with side reactions, including epimerization.
- TCFH and N-methylimidazole (NMI) are economical and practical reagents to react carboxylic acids with amines, alcohols, and thiols to form amides, esters, ketones, and thioesters.
- TCFH /OxymaPure are highly reactive, inexpensive, and safe reagent combinations for the coupling of hindered amines.
Studies
- TCFH – a safe, affordable reagent for ester and difficult amide synthesis
Read Article - Rapid Development of a Commercial Process for Linrodostat, an Indoleamine 2,3-Dioxygenase (IDO) Inhibitor
Kenneth J. Fraunhoffer, Albert J. DelMonte, Gregory L. Beutner, Michael S. Bultman, Kathryn Camacho, Benjamin Cohen, Darryl D. Dixon, Yu Fan, Dayne Fanfair, Adam J. Freitag, Andrew W. Glace, Francisco Gonzalez-Bobes, Manjunath Gujjar, Matthew W. Haley, Matthew R. Hickey, Jeanne Ho, Vidya Iyer, Prantik Maity, Sunil Patel, Victor W. Rosso, Michael A. Schmidt, Jason M. Stevens, Yichen Tan, Christopher Wilbert, Ian S. Young, and Miao YuOrganic Process Research & Development 2019 23 (11), 2482-2498
- TCFH–NMI Ketone Synthesis Inspired by Nucleophilicity Scales
Johnson H. Ho, Grant H. Miller, Kasey K. Chung, Sydney D. Neibert, Gregory L. Beutner, and David A. VosburgOrganic Letters 2024 26 (41), 8904-8909
- General chemoselective hindered amide coupling enabled by TCFH-catalytic Oxyma and transient imine protection Li, Qiuhan and Napier, Sarah and Singh, Andrew N. and Vickery, Thomas P. and Fan, Yi and Hernandez, Edgar and Wang, Tao and Dalby, Stephen M.,
Chem. Commun. 2025 61 (4), 721-724.
http://dx.doi.org/10.1039/D4CC05313C