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