Method of obtaining urethane-protected N-carboxyanhydrides of alpha amino acids

A method for obtaining urethane-protected N-carboxyanhydrides of alpha amino acids (UNCAs), of formula I

• in which R1 and R2 are either identical or different, and selected from the group consisting of a hydrogen, a C1-C8 linear or branched alkyl, a C5-C7 cycloalkyl, a phenyl, napthyl, 5- or 6-membered heteroaromatic, and indole, wherein R1 and R2 may optionally be substituted with a customary substituent in the field of amino acids and peptides, wherein the substituent is selected from the group consisting of OH, SH, NH2, NHC(NH)NH2, CONH2, O—(C1-C6 aryl), S—(C1-C6 alkyl), COO—(C1-C6 alkyl), and COO—(C5-C8 aralkyl), with the proviso that R1 and R2 do not each represent a cyclic simultaneously;
• or R1 and R2 forms together a C5-C7 cycloalkyl, and
• R3 is selected from the group consisting of a saturated or unsaturated, linear or branched C1-C10 alkyl, an aralkyl with 7 to 14 carbon and an alkylaryl with 7 to 14 carbon atoms, comprising the step of reacting an N-carboxyanhydride of alpha-amino acid (NCA) of formula II,
• in which R1 and R2 have the same meaning as for the formula I, with at least one equivalent, relatively to the molar amount of the N-carboxyanhydride of alpha-amino acid (NCA) of formula II, of a dicarbonate of formula III
• in which R3 has the same meaning as for the formula I, in the presence of a catalytic amount of triethylene diamine (TEDA), relatively to the molar amount of the N-carboxyanhydride of alpha-amino acid (NCA) of formula II, in an organic solvent with a melting point less than about −20° C.