We have a BOC-protected amino acid, in which the carboxylic acid is in the form of an active ester with N-hydroxysuccinimide. We wish to couple to a free amine, in which the C-terminus is protected as the tertiary-butyl ester. We have been searching the literature for conditions. We found about 30 reactions via SciFinder, plus one other from a previous search, of which most were in the patent literature. DMF shows up a good deal as the solvent, but I have also seen THF and DCM. The biggest puzzle is the presence and the amount of tertiary amine base which is present more often than not (triethylamine, DIPEA, or N-methylmorpholine being employed in most instances). In some instances, the amine was used as a hydrochloride or hydrobromide salt, but this is not stated clearly in every example. In one instance in which the hydrobromide salt was used, there was a 4.67 mole excess of TEA present. There might have been traces of acetic acid left in this particular example, but I am not sure.
My main question is whether or not we should include a tertiary amine base. A nonnucleophilic base would be unlikely to do harm, but I am not sure if will do any good (unless we have some acid as an impurity. My second question is the choice of solvent. I am inclined to go with DMF but am open to other ideas. I may try a search with slightly more relaxed criteria later. Thanks for any ideas.