[nurban]

I was wondering why some people do EDC/HOBt coupings at 0 degrees and some people do them at room temperature. I can't find any references that discuss this and none of the papers i've read mention why they choose a particular temperature. Any ideas?

[Markov]

Well, my guess is that people run it at 0C as a first try. If it works at 0C, I would also keep it there.

I know that some "activated ester" analogues are somewhat thermally unstable and that's why I wouldn't heat it up unless needed.

E.g some mixed anhydrides from isobutyl chloroformiate have a survival of just an hour or two, even at 0-5C.

It would be interesting to know if somebody has a rough idea about the thermal stability of EDC/HOBt-intermediates.