9-Fluorenylmethyl chloroformate reaction with amino acids

A second amino protecting group, the 9-fluorenylmeth xycarbonyl protecting group, abbreviated as Fmoc, is formed by reacting the amino acid with 9-fluorenylmethyl chloroformate in a nucleophilic acyl substitution reaction. 

It was soon realized that major side products in this reaction are the corresponding Fmoc dipeptides (and even tripeptides) at extents of 1-5%, occasionally up to 14%. This side reaction occurs via a multistep mechanism involving, (1) Fmoc protection (2) formation of a noixed anhydride with excess 9-fluorenylmethyl chloroformate (17) and (3) peptide coupling with unreacted amino add.f " The formation of Fmoc dipeptides is particularly favored with nonhindered amino acids, e.g. in the case of glycine 14.4% dipeptide and 0.2% tri-... 

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