What are the options that I might be missing for the purification of a molecule with the following characteristic:
- Contains an activated ester that reacts with water (NHS)
- Reacts readily with alcohols
- Does not elute on silica gel (typical or spherical) with THF, Acetone, EtOAc, DCM, or Acetonitrile
- Is not a solid that can be precipitated, rather some horrible gum
- Decomposes rapidly in prep-LC on C18 0.1% TFA (10% back to acid after 20min run in best cases) typical loss of material is about 50% from initial mass.
- Greasiest solvent that solubilises is DCM
Impurities are mainly side product from NHS coupling reagents or relatively uncharacterized impurities with properties similar to final product.
Honestly, I have not much hope left to find something there but if you know of conditions what could provide separation in reverse phase HPLC with aprotic solvent, I'm all ears.
Edit: I'm open also to hear about volatile buffer system that could be in a pH range that would allow greater stability of the NHS in water.