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

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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

J. Org. Chem., 2006, 71 (24), pp 9045–9050

DOI: 10.1021/jo061377b

Publication Date (Web): October 28, 2006

To whom correspondence should be addressed. Fax: 1-860-715-7305.

†

Present address: Ann Arbor Laboratories, Pfizer Global R&D, Ann Arbor, MI 48105.

, bryan.li@pfizer.com

Abstract

Aqueous phosphoric acid (85 wt %) is an effective, environmentally benign reagent for the deprotection of tert-butyl carbamates, tert-butyl esters, and tert-butyl ethers. The reaction conditions are mild and offer good selectivity in the presence of other acid-sensitive groups, including CBZ carbamates, azetidine, benzyl and methyl esters, TBDMS, and methyl phenyl ethers. The mildness of the reaction is further demonstrated in the synthesis of clarithromycin derivative 4, in which a tert-butyl ester is removed in the presence of cyclic carbamate, lactone, ketal, acetate ester, and epimerizable methyl ketone functionalities. The reaction preserves the stereochemical integrity of the substrates. The reactions are high yielding, and the workup is convenient.

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Published In Issue November 24, 2006
Received July 3, 2006

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Article

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