[The Guy]

Hi All

I am runing the column with 30% EtOAc, then 50%, then 100% EtOAc.
My problem is, several time I tried to dissolve the thick crude to run it through the column, but it only dissolve with EtOAc which result part of the product comes first out of the column and the rest at the end. I tried to dissolved it in 30% EtOAc but I got precipitant. Is it ok to dissolve it with 100% EtOAc or CH2Cl2 and run the column starting with 30%?
I am using silica gel, and it is small column, I pack it like 5cm high and .5 cm diameter.

the attached molecules, would guess it will elute with 30% EtOAc, or it is too polar?

[hypervalent_iodine]

Your amine may be giving you problems here. It might be worth investigating something like 5% MeOH in DCM via TLC. Chloroform could also work in place of DCM, though I tend to prefer DCM myself.

[clarkstill]

I've had problems with similar molecules that contained many flat aromatic rings, they tend to have very poor solubility.  As for your column, DCM is probably a good bet: hopefully it will easily dissolve your compound so the elution reflects polarity not solubility. 

You could also try dry-loading your compound onto silica so you don't have to use a large amount of polar solvent to make it dissolve: this involves dissolving your compound in a good (volatile, e.g. DCM) solvent along with a small amount of silica, then vaccing off the solvent (with an anti-bumping flask padded with cotton wool to prevent loss of the silica).  Once the solvent is gone the silica should become free-flowing, and you can load it directly with your compound adsorbed on its surface.

[The Guy]

Thank you for your help.

I will try that.

What about the solvent extraction, do you think EtOAc would work well? or DCM is better with mu product?

[clarkstill]

When I'm desperate I use 3:1 chloroform:isopropanol for extraction - it seems to pull a lot more out of the aqueous phase than either dcm or ethyl acetate alone.  You can always TLC your aqueous layer/your extractions to ensure you aren't leaving any product behind. Good luck!