Hi guys, I'm using DIPEA/HOBt to couple my amides. The products are there but there are unnecessary intermediates or spots that appearing on the TLC plate. I tried filtering & flash purification but to no avail. What can I do to remove the intermediates? I had lost all my crudes while performing a flash chromatography (automated one, not a column/traditional method because the process is usually even slower in that one.) I test them under MeOH/DCM solvent system (between 5-10% MeOH). However, upon flash, the product doesn't come out. What can I do other than flash to remove those top intermediate ester spots? Any tips?
If you don't have a large amount of material, the easiest way would probably be to do a prep TLC, because you already know that you will get separation with that technique.
What solvent system did you run for your TLC plates? It should run in a column with the same solvent system. One common problem is often, a spot will run most of the way up the TLC plate. Using the same solvent system in a column causes the compound to elute at the void (1 column volume). As you mentioned the compound didn't elute, this suggests another problem. Did you try a gradient to try to wash your compound out? Another possibility is that the TLC plate has adsorbed some moisture, and is "deactivated". Saturating the solvents used for the column with water, and allowing a long equilibration, may allow elution.
Assuming you did try a gradient, your compound may be decomposing in the column; this could happen if the pH of the column is different from that of the TLC plate. You can try another stationary phase such as alumina, diol, or cyano which may be less reactive.
One last detail- it doesn't matter if the solution is clear, so long as your compound dissolves. It has to be soluble in the mobile phase because to run in any chromatographic system (TLC or a column), the compound needs to partition between the mobile phase and stationary phase. If it were insoluble in the mobile phase, the compound can't elute because the equilibration would be 100% on the stationary phase!
Jack Silver Thanks for the recommendation.
I first use 5% MeOH in DCM later I increase the polarity to 8% MeOH for TLC purposes. I do use gradient table on the flash instrument in my lab. Thanks & I will give it a try on my next set of rxns. The separation does occur but they are partially dissolvable in MeOH or other solvent. I have figured that flash is my last resort to remove the ester-amide intermediates.
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