Microwave-assisted protection of primary amines as 2,5-dimethylpyrroles and their orthogonal deprotection.
Primary amines can be readily doubly protected as N-substituted 2,5-dimethylpyrroles. Although this protecting group is stable toward strong bases and nucleophiles, long reaction times are required for both the protection and deprotection steps, generally resulting in low deprotection yields. By employing microwave irradiation, protection and deprotection reaction times are dramatically reduced. Furthermore, deprotection with dilute hydrochloric acid in ethanol increases reaction yields. Diverse deprotection conditions have been developed in conjunction with microwave irradiation, so that protection as an N-substituted 2,5-dimethylpyrrole can be orthogonal to other standard amine protecting groups, such as tert-butyloxycarbonyl (Boc), carbobenzyloxy (Cbz), and 9-fluorenylmethyloxycarbonyl (Fmoc).
Department of Chemistry, Chemistry of Life Processes Institute, and Center for Molecular Innovation and Drug Discovery, Northwestern University , Evanston, Illinois 60208, United States.
Amit
A
Walia
Soosung
S
Kang
Richard B
RB
Silverman
D000588:Amines / Q000737:chemistry*; D005449:Fluorenes / Q000737:chemistry; D005563:Formic Acid Esters / Q000737:chemistry; D008872:Microwaves; D015394:Molecular Structure; D011758:Pyrroles / Q000737:chemistry*
C496789:9-fluorenylmethoxycarbonyl; D000588:Amines; D005449:Fluorenes; D005563:Formic Acid Esters; D011758:Pyrroles; C000345:t-butyloxycarbonyl group; C067286:2,5-dimethylpyrrole