Journal Article
Aqueous phosphoric acid as a mild reagent for deprotection of tert-butyl carbamates, esters, and ethers
Li, B; Berliner, M; Buzon, R; Chiu, CK; Colgan, ST; Kaneko, T; Keene, N; Kissel, W; Le, T; Leeman, KR; Marquez, B; Morris, R; Newell, L; Wunderwald, S; Witt, M; Weaver, J; Zhang, Z; Zhang, Z
Journal of Organic Chemistry
ISSN: 0022-3263
EISSN: 1520-6904
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, 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.
Esters; Ethers; Ketones; Stereochemistry; Synthesis (chemical); Carbamates; Methyl esters; Stereochemical integrity; Phosphoric acid; acetal; acetic acid ester; acetone; anisole; anisole derivative; azetidine; benzyl derivative; carbamic acid derivative; clarithromycin derivative; ester derivative; ether derivative; lactone; phosphoric acid; reagent; aqueous solution; article; chemical analysis; chemical reaction; chemical structure; deprotection reaction; drug synthesis; stereochemistry; structure analysis; Carbamates; Esters; Ethers; Indicators and Reagents; Magnetic Resonance Spectroscopy; Phosphoric Acids; Water