title: Aqueous phosphoric acid as a mild reagent for deprotection of tert-butyl carbamates, esters, and ethers.
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, 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.
authors.affiliation: Groton Laboratories, Pfizer Global Research and Development, Groton, Connecticut 06340, USA. bryan.li@pfizer.com
authors.forename: Bryan
authors.initials: B
authors.lastname: Li
authors.forename: Martin
authors.initials: M
authors.lastname: Berliner
authors.forename: Richard
authors.initials: R
authors.lastname: Buzon
authors.forename: Charles K-F
authors.initials: CK
authors.lastname: Chiu
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Colgan
authors.forename: Takushi
authors.initials: T
authors.lastname: Kaneko
authors.forename: Nandell
authors.initials: N
authors.lastname: Keene
authors.forename: William
authors.initials: W
authors.lastname: Kissel
authors.forename: Tung
authors.initials: T
authors.lastname: Le
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Leeman
authors.forename: Brian
authors.initials: B
authors.lastname: Marquez
authors.forename: Ronald
authors.initials: R
authors.lastname: Morris
authors.forename: Lisa
authors.initials: L
authors.lastname: Newell
authors.forename: Silke
authors.initials: S
authors.lastname: Wunderwald
authors.forename: Michael
authors.initials: M
authors.lastname: Witt
authors.forename: John
authors.initials: J
authors.lastname: Weaver
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zhongli
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D002219:Carbamates / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*; D004987:Ethers / Q000737:chemistry*; D007202:Indicators and Reagents / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010756:Phosphoric Acids / Q000737:chemistry*; D014867:Water
chemical_list: D002219:Carbamates; D004952:Esters; D004987:Ethers; D007202:Indicators and Reagents; D010756:Phosphoric Acids; D014867:Water; C030242:phosphoric acid