During workup, I extracted a product 2x into ethyl acetate (from i-PrOH/water) and concentrated to a yellow powder. Ensuing purification of the crude has proven difficult as the powder does not easily dissolve in many solvents/mixtures including EtOAc, MeOH, H2O and DMSO. The crude does dissolve in DMSO with heating, but precipitates out upon cooling, with impurities.
My first thought was crystallization, but I had no success and was only able to precipitate a fine powder from DMSO/MeOH with unacceptable purity (~80%). I assumed that chromatography would be problematic, and expected the product to crash out on the column. However, TLC showed the product moved very well in EtOAc:MeOH, (9:1, Rf~0.7) so I gave it a shot using 3% MeOH. I loaded the DMSO sample onto a short column and the product band got halfway down before crashing out as soon as it separated from the DMSO, as expected.
So I have two questions, 1) any ideas on how to get the compound off the column?* and 2) any ideas on a better purification for the difficult to dissolve product?
I'm leaning toward trying precipitation, filtering, and washing with hot MeOH, but I'm not excited about the expected yield of purification from that method, since this product is 4 steps down a synthesis I'd rather not restart on larger scale to accommodate a 10% yield step.
*This was conducted on 20mg scale, in preparation for scale up. I'm not terribly concerned with the product on the column, but would like to establish a reliable purification method before burning my precursor.