[chonfusion]

Hi,

I need to acylate a diamine with an activated acid. The product came as a HCl salt and simply adding TEA in excess did not give me the best yield with acid NHS ester. Should I convert it to free amine first using Ethanol-NaOH followed by filtration to remove NaCl, or through more costly ion exchange column?  I try to stay away from converting it to free amine in aqueous NaOH then extract it back because its solubility is too high in water.  Thank you!

[Squirmy]

What do you plan to do with the amine after you isolate it?

If its fate is another reaction, have you considered taking the HCl salt through and generating the free amine during that reaction?

[chonfusion]

Thanks! Once I convert it to di-amide I will do purification and other reactions.

yes. I added an excess amount of TEA to neutralize the proton and the solubility of the amine salt was low, and the reaction did not go anyway. I have tried THF, MeOH and DMF, none has worked. Maybe I should try it in water with base? The acid and the product are not water soluble though.

[Squirmy]

Oh, you want the di-amide! I misunderstood and thought you were trying to selectively acylate one amine. Sounds like that's happening, but that's not what you want. Correct?

How precious is your activated acid? You might consider phase transfer catalysis if it's cheap or readily available (some of it will be hydrolyzed).

[StarvinMarvin]

after the reaction you can just dissolve it in MeONa. Just add some sodium to MeOH, dissolve the product and then filter off the NaCl. This method works of course provided that MeONa would not attack anything else in the structure. And this way you wouldn't need to use water. Afterwards you can just neutralize it, filter it and evaporate the methanol.