Aqueous Phosphoric Acid as a Mild Reagent for Deprotection of tert-Butyl Carbamates, Esters, and Ethers

Bryan Li,* Martin Berliner, Richard Buzon, Charles K.-F. Chiu, Stephen T. Colgan, Takushi Kaneko, Nandell Keene, William Kissel, Tung Le, Kyle R. Leeman, Brian Marquez, Ronald Morris, Lisa Newell, Silke Wunderwald, Michael Witt, John Weaver, Zhijun Zhang and Zhongli Zhang

*Groton Laboratories, Pfizer Global Research and Development, Groton, Connecticut 06340, E-mail: bryan.lipfizer.com

B. Li, M. Berliner, R. Buzon, C. K.-F. Chiu, S. T. Colgan, T. Kaneko, N. Keene, W. Kissel, T. Le, K. R. Leeman, B. Marquez, R. Morris, L. Newell, S. Wunderwald, M. Witt, J. Weaver, Z. Zhang, Z. Zhang, J. Org. Chem., 2006, 71, 9045-9050.

DOI: 10.1021/jo061377b

---

Abstract

Aqueous phosphoric acid is an effective, environmentally benign, selective and mild reagent for the deprotection of tert-butyl carbamates, tert-butyl esters, and tert-butyl ethers. CBZ carbamates, azetidine, benzyl and methyl esters, TBDMS, and methyl phenyl ethers are tolerated. The reactions are high yielding, and the workup is convenient.

see article for more examples

---

---

Comments

The reaction typically takes 3 - 14 hours. The preferred solvent is toluene (1 mL/g substrate ideally). If one has to handle mg quantity, 0.5 mL of solvent and 0.5 mL of 85% H₃PO₄ can be used.

Bryan Li, Mai 25, 2006

---

Key Words

tert-butyl carbamates, tert-butyl esters, tert-butyl ethers

---

ID: J42-Y2006-3830