aka “Clowns to the left of me, jokers to the right”

This post isn’t about the “best” way to run an extraction – that will be a whole series of posts, sometime in the distant future – it’s about a specific method.  A couple of years back I needed large quantities of a certain reagent (>10g), which wasn’t really commercially available.  It could be synthesized in a single step (below), but unfortunately the purification was a bit of a pain.  The literature called for flash chromatography in a chloroform/methanol/ammonia mix; a nasty but serviceable.  But the compound bled on the column, and after several hours of work and several litres of carcinogenic solvents all we had was a small amount of the needed material.  To add insult to injury, the product is rather efficient at removing CO2 from the atmosphere.  Let it stand for a little while and you end up with a less-than-useful white sludge.           So, some modifications to the procedure were needed.  Pre-column the crude material was composed of only three compounds: unreacted 1,4-diaminobutane (putrescine, named for its distinct odor), tert-butyl 4-aminobutylcarbamate, and di-tert-butyl butane-1,4-diyldicarbamate (according to chemdraw).  The Boc2O was consumed in the reaction, and both the t-butanol byproduct and triethylamine were readily removed under vacuum, though we normally removed the butanol in an extraction pre-column.  Stretching back to second year organic chemistry we supercharged the extraction step, and chem up with this gem of a flow chart.

It’s not something you think about every day, but each of the three common extracting solvents has a different extraction efficiency.  Ethyl acetate is the strongest, able to pull highly polar compounds out of simple water, and the rest flow down in polarity, like so:

EtOAC > DCM > Et2O >> Hexanes

It took a little trial and error to find the appropriate choice for each step (ethylacetate, for example, will draw out putrescine as well as the desired product in the last step), but in the end that was time well spent.  In the updated procedure there’s no column, the whole process takes about thirty minutes, and we obtain at least 90% of the mono-Boc product at the end, pure by NMR.  There’s also the option of getting the two impurities as pure compounds along the way, should we want them.

The double extraction requires at the least an acid or base, so it’s not generally applicable.  It does make a good ace in the hole though, when little else works.

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