Di-tert-butyl Dicarbonate - Protection and Deprotection of Amines

Protection and Deprotection of Amines

The Boc group can be added to the amine under aqueous conditions using di-tert-butyl dicarbonate in the presence of a base such as sodium bicarbonate. Protection of the amine can also be accomplished in acetonitrile solution using 4-dimethylaminopyridine (DMAP) as the base.

Removal of the t-BOC in amino acids can be accomplished with strong acids such as trifluoroacetic acid neat or in dichloromethane, or with HCl in methanol. A complication may be the tendency of the t-butyl cation intermediate to alkylate other nucleophiles; scavengers such as anisole or thioanisole may be used. Selective cleavage of the N-Boc group in the presence of other protecting groups is possible when using AlCl₃. The use of triethylsilane as a carbocation scavenger in the presence of trifluoroacetic acid in dichloromethane has been shown to lead to increased yields, decreased reaction times, simple work-up and improved selectivity for the deprotection of t-butyl ester and t-butoxycarbonyl sites in protected amino-acids and peptides in the presence of other acid-sensitive protecting groups such as the benzyloxycarbonyl, 9-fluorenylmethoxycarbonyl, O- and S-benzyl and t-butylthio groups(ref 9).