Hello Kimi, EDC could be used in water, but the procedure is different (typically in combination with NHS). The reaction is quite sensitive to pH. Please read the publication below.

Article A Method for the High Efficiency of Water-Soluble Carbodiimi...

Thank you sir. But my question is that EDC in combination with DMAP can be employed in DCM and DMF. Why DMAP cannot be combined with EDC in water as solvent? More specifically i am asking about the effect of solvent in this reaction.

From the publication above: "The formation of O-acylurea occurs optimally at pH 4-5; the intermediate has an extremely short half-life and rapidly undergoes hydrolysis or rearranges to give the N-acylurea adduct."

pKa of DMAP in water is about 9.6, which means pH will be quite alkaline. Hence O-acylurea intermediate is very likely to be hydrolyzed before the reaction with an amine can take place!

thanks, i work with different solvents on amide synthesis using EDC/dmap/ hobt(cat), the good yield obtained by the use of acetonitrile and 2 eq DIPEA.

i agree with the researcher notes about the use of water with EDC.

a note i found during small scale work, working with acid and base lead to heavy loss of the final product and its better to perform short coloumn if ur compound not sensitive to silica.

thanks and regards