[synthon]

I know this is not a unique problem and has been generally covered in archived posts, but I'm having trouble getting a polar compound pure.  It's an organic anion and I see great separation on RP-HPLC from the main (only UV active) contaminant, but attempts to crystallize have been unsuccessful, as have TLC (not mobile), anion-exchange (won't stick to column), and RP chromotography on a Sep-Pak (no separation).  I don't have access to RP silica to run a proper column, or the time to run a prep HPLC for the amount of product req'd.

I'm nearly at my wits end with this today, and hoping to find some suggestions here to strengthen my resolve, so all help is welcome.  All I can think is to do now is continue to try and crystallize from various solvents.

Sorry for the somewhat repetitive post.

[discodermolide]

Run a normal phase column to remove the UV active compound, then elute yours off the column and try and crystallise it.
I assume the UV active component runs on normal phase?

[synthon]

Neither compound moves in normal phase on TLC.  Well, they move, together in MeOH with an Rf of ~0.3

[discodermolide]

OK remove the UV impurity by reverse phase, then get your compound off the column and crystallise it.

[synthon]

That would be my next choice if I had RP silica, although the products move pretty close together.  However, I only have access to C18 Sep-Paks which apparently don't give near the req'd separation.  I thought about connecting about 10-20 of them together to get the desired effect, but I'm not sure that will fly....or even work.

[discodermolide]

In that case you are left with crystallization attempts.

[synthon]

Fun.  I also only have about 25-30 mg of product, so add that to the difficulty level. I'll update if I have any success.

[discodermolide]

Good luck

[Babcock_Hall]

Two questions.  Why won't the compound stick to ion-exchange resins?  Is the impurity also an anion?

[OC pro]

Fun.  I also only have about 25-30 mg of product, so add that to the difficulty level. I'll update if I have any success.

I assume you have no access to semipreparative HPLC?

[Dan]

Synthon, try TLC with the following eluents:

45:5:1 EtOAc/EtOH/H₂O

7:2:1 EtOAc/IPA/H₂O

If it won't move in those, I don't think you are going to be able to column it on silica.

Any structural info you can give us is useful. Certain functional groups may call for certain doping agents etc.

[Babcock_Hall]

We also have some moderately polar products.  They are amides between BOC-Orn or BOC-lysine and nicotinic or isonicotinic acid.  The solvent systems 45:5:1 EtOAc:EtOH:H2O or 80:20 Acetone:MeOH both provided R_fs for our product (~0.2), and separation from the chief impurity, which is para-nitrophenol.  Should we use as is, or should we tweak one of them to move our product more quickly?

[discodermolide]

I would leave it as it is. After the main impurity is off the column then (if there are no others) increase the polarity slightly and you will move your product.

[408]

I am currently using MeOH MeCN benzene 50:50:10 and it moves an organic, highly polar heterocyclic anion I am working with.  Try a TLC

[Babcock_Hall]

Do you mean 50:40:10?  Could toluene be substituted for benzene?