Question

Acid Amine Coupling with edc.hcl procedure. Plz explain.

Answer 1

Change the addition order, have DMAP, Acid and Amine stirring in DCM then add the EDC dropwise.

The major side products for diimide coupling reagents in the absence of an amine are acyl transfer to form the N-acylurea, and formation of the symmetric anhydride. Together with the desired O-acylisourea intermediate this could account for your three spots (assuming none of those are starting material or the urea side product).

Addition of HOBt will suppress acyl transfer.

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