The selective removal of protecting groups is of critical importance in many synthetic sequences. The more selectively a protecting group can be removed, the more useful it becomes. We report here an efficient method for the selective removal of an N-BOC protecting group in the presence of a tert-butylester and several other common protecting groups.During the course of earlier synthetic work,l it became necessary to remove an N-BOC while retaining a tertbutyl ester. Review of the literature revealed only one example of this transformation,2 which we found to be slow and limited in scope. Examples of rapid N-BOC removal with dry HC1 in ethyl acetate3 are known, and we considered that this might give the desired selectivity. Treatment of N-BOC-aminoadipic acid tert-butyl ester derivative la with a large excess of dry HC1 in EtOAc for 3 h did indeed give the selective deprotection desired in 97 5% yie1d.l Further investigation established that as little as 500 mol % of a 1 M HC1 in EtOAc solution would efficiently remove an N-BOC within 5 h at rt. In most cases, the product hydrochloride precipitated during the course of the reaction, possibly helping limit tert-butyl ester removal. The deprotection was carried out on a variety of N-BOC amino acid tert-butyl esters and derivatives, as shown in Table 1.Each tert-butyl ester N-BOC amino acid derivative was treated under the same standard conditions, namely it was dissolved in a dry 1 M solution of HC1 in EtOAc containing 500 mol 5% of HC1. The reaction mixture was stirred at rt until TLC indicated complete consumption of N-BOC tert-butyl ester 1. S-and N-BOC protected cysteine and homocysteine tert-butyl esters lm and In were each treated with lo00 mol % of HC1 to affect efficient cleavage of both the S-and N-BOC groups. In each case, amine hydrochloride product 2 was isolated either by filtration or after evaporation of the reaction mixture. Product hydrochlorides were usually analytically pure4 and could be used without further purification.Several results point out additional selectivity for this method. tert-Butyl ethers tyrosine lg and serine lk demonstrated the greater acid sensitivity of an aryl tertbutyl ether versus an alkyl tert-butyl ether. While the phenolic ether in tyrosine lg was completely cleaved within (1) Bergmeier, S. C.; Cobas, A. A.; Rapoport, H. J. Org. Chem. 1993, (2) Goodacre, J.; Ponsford, R. J.; Sterling, I. Tetrahedron Lett. 1975, (3) Muraki, M.; Mizoguchi, T. Chem. Pharm. Bull. 1971,19, 1708.(4)Products were greater than 95% pure as judged by NMR spectroscopy, and typically gave correct C, H, and N analyses upon drying.
58, 2369.
3609.Table 1. Amino Acid tert-Butyl Ester Hydrochlorides 2 from N-BOC Substrates 1 ~ ~ ~~ 7% entry N-BOC tert-butyl esters 1 products 2 yield d 0 BOCN W O B d \sN HNBOC e ' f 4 2 1 R e, R = H f, R = CHO g 'BuO 0 BOCNH h , R = H j,R=trityl h-k RO+OW 1, R = TBS k, R =But 1, m 0 RS+OBU~ BOCNH I, R -triiyl m, R I BOC n Bocs&OBul BOCNH e,R=H 1. R = CHO I, R -trityl, R' = NH3+ CIm, R = H, R -NH, + CI' 0 NH,+CI' Bocs+OB...