[benjamin5476]

I think that in before purification you should use the method of chemistry removed some of its impurities，I think that use physical method to remove impurities efficiency is not high.

[synthon]

Sorry to have ignored this thread for so long, but since it's active again...

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

I think the anion may be too weak, but it could be a problem with my procedure.  After prepping the column, loading my crude product, and washing with water, all the crude comes out in the first fraction.  The impurity is HOBt.

...try TLC with the following eluents:

45:5:1 EtOAc/EtOH/H2O

7:2:1 EtOAc/IPA/H2O

...MeOH MeCN benzene 50:50:10...

With EtOAc/EtOH/H2O, the HOBt moves at Rf 0.2, the product not at all.

MeOH MeCN benzene moves the product well, with some separation from HOBt (Rf 0.4, compared to 0.5).  Seems like this system would wash out silica pretty fast, though.  Maybe not.

I had pretty good success using RP Sep-Paks in series, eluting with water, then ethanol.  But I've just changed to DMAP instead of HOBt in repeating the coupling, so that I can simply wash it out with DCM.  I'm hoping that helps, and I'll test a mini-column on the crude product of the first rxn.

Thanks for all the suggestions.

[408]

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

I mean what I said, I realize it does not add up to 100% but it is experimentally determined.  toluene: probably, I never tried it.  Gut says it will not work as well, but should be close.

MeOH MeCN benzene moves the product well, with some separation from HOBt (Rf 0.4, compared to 0.5).  Seems like this system would wash out silica pretty fast, though.  Maybe not.

Awesome, pretty much what I expected but I was hoping for more separation.  Up the benzene 10% removing equally from MeCN and MeOH and TLC again, should increase separation.

Alternatively, try 50:45:10:5  MeOH:MeCN:benzene:pyridine.  yes we are getting into 4 solvents.  s#*$ just got real.

yeah, some silica always comes through.  but that can always be removed later. 

EDIT: Hah!  just realized HOBt is hydroxybenzotriazole!  not totally unlike the s#*$ I do.  try the above systems.  My confidence in my TLC mixture improvements has increased significantly.  report back after TLC and let me know how it worked.

Also: WTH is a sep-pak?

[Dan]

With EtOAc/EtOH/H2O, the HOBt moves at Rf 0.2, the product not at all.

Did you try the 7:2:1 EtOAc/IPA/water?

Silica dissolution is not bad with that system.

[Babcock_Hall]

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

I mean what I said, I realize it does not add up to 100% but it is experimentally determined.  toluene: probably, I never tried it.  Gut says it will not work as well, but should be close.

I see what you mean now; those numbers are probably volumes, not percentages.  Toluene will be a little more difficult to remove, but it is much less toxic than benzene.  A sep pak is used for solid phase extraction.  Many are based on C18.  http://www.waters.com/webassets/cms/library/docs/wa20300.pdf