What are the options that I might be missing for the purification of a molecule with the following characteristic:

  1. Contains an activated ester that reacts with water (NHS)
  2. Reacts readily with alcohols
  3. Does not elute on silica gel (typical or spherical) with THF, Acetone, EtOAc, DCM, or Acetonitrile
  4. Is not a solid that can be precipitated, rather some horrible gum
  5. 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.
  6. 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.

  • $\begingroup$ How does it behave on alumina? $\endgroup$ – Waylander Jul 7 '17 at 16:39
  • $\begingroup$ Haven't checked. I always thought it was rather similar to silica gel but really inconvenient. Would you expect a different result? The core structure look like silica gel a lot. I'll try to find tlc for that... $\endgroup$ – user46680 Jul 7 '17 at 17:15
  • 1
    $\begingroup$ Alumina can give different results so it is worth checking. Do you have access to the range of 'flavoured' silicas? Those can also give useful differentiation between substrates. $\endgroup$ – Waylander Jul 7 '17 at 17:50
  • $\begingroup$ I can get pretty much anything, but I would like to get tlc before committing my product. $\endgroup$ – user46680 Jul 7 '17 at 17:52
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    $\begingroup$ You can get tlc plates of the various favoured silicas $\endgroup$ – Waylander Jul 7 '17 at 19:42

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