N-(4-Nitrophenylsulfonyl)- and N-(Fluorenylmethoxycarbonyl)-N-ethyl Amino Acid Methyl Esters – A Practical Approach

An efficient one-pot preparation of N-ethyl-N-4-nitrophenylsulfonyl (nosyl) amino acid methyl esters was accomplished by a simple N-ethylation reaction by using triethyloxonium tetrafluoroborate in the presence of N,N-diisopropylethylamine. The N-ethylated amino acid methyl esters are obtained with total retention of stereochemistry at the original chiral centers. To further broaden the scope of this methodology, the N-ethylated nosyl-protected compounds are easily converted in the more practical fluorenylmethyloxycarbonyl (Fmoc)-protected derivatives. The cleavage of methyl ester by using a mild and neutral method enables the preparation of N-ethyl amino acids that are building blocks suitable for introduction into a peptide chain. The methodology works well with both nosyl- and Fmoc-based solution-phase peptide synthesis.