Large scale Curtius rearrangement
The Curtius rearrangement, discovered by Julius Wilhelm Theodor Curtius in 1885, is the thermal decomposition of an acyl azide to an isocyanate with loss of nitrogen gas. This versatile transformation has been widely used in organic synthesis to convert a carboxylic acid to an amine with the loss of a carbon atom. [1] Very recently, this rearrangement has been used for the large scale synthesis of a potent irreversible covalent inhibitor of KRAS?12?, as outlined in the Scheme below. [2]
[1] For an excellent review, see: (a) A. K. Ghosh, M. Brindisi, A. Sarkar, ChemMedChem 2018, 13, 2351-2373.
[2] G. Zuo, H. Xu, Y. Zhang, Z. Liu, J. Tu, D. Gou, P. Fu, H. Huang, J. Ren, Y. Hu, F. Liu, J. J. Li, G. Zhang, Org. Process Res. Dev. 2024, 28, 3871-3882.
Chemist in Medicinal Chemistry
1 周The most interesting is the formation of a protected amine (carbamate) in one step via the isocyanate intermediate (exceptionally helpful), thanks
PhD organic and medicinal & polymer chemistry
1 周Very helpful
Founder @ RSCHEMTREE | PhD in Synthetic Organic Chemistry, Indian Institute of Science, Bengaluru, India
1 周Agree.. sorry for the error
Founder @ RSCHEMTREE | PhD in Synthetic Organic Chemistry, Indian Institute of Science, Bengaluru, India
1 周In large scale, Lawson's rearrangement - ester to amine with hydroxylamine- works better. No safety issues