[baum0372]

Hi Everyone,

I have an amine that I am trying to extract out of the aqueous phase, but it's pretty stubborn and really seems to like the aqueous phase (I can get some out in ethyl acetate with a pH=12 aqueous layer, but not all of the product I expect).  I have tried other ways to purify this amine (column, recrystallization) but I have heard that there are some techniques one can use to help move organic products into the organic phase.

I have heard that adding brine, or LiCl, or even MeOH can help move stubborn products into the organic phase.  Are these true? And what other techniques are there that I can use?

Thanks.

[discodermolide]

You need the free amine? If not make the HCl salt, remove water on rotavap. and crystallise it.

[baum0372]

Thanks for the suggestion, but actually I have the amine as the TFA salt right now.  I do want to try and isolate the free amine if possible.

Thanks.

[discodermolide]

Ethyl acetate at pH 12 will start to hydrolyse, it may be better to use an ether like TBME. You can always do a continuous extraction. Adding salts to the aqueous layer will help, NaCl (saturated) is usually employed.

[wildfyr]

Definitely try brine, then LiCl if that doesn't work. Why does it have to remain protonated during the extraction? It would be MUCH easier to move to the organic layer unprotonated, Have you neutralized (or made basic) the solution then tried a conventional extraction?

[baum0372]

Thanks for the reply wildfyr,

Actually I have deprotonated the amine.  I have tried to pull it (150mg) out of the aqueous layer by adding saturated brine solution (10mL) and also 1N NaOH (5mL).  After several extractions with ethyl acetate and even DCM, I can only recover trace residue in the flask.  The amine I am working with is the imide product of exo-norbornene-2,3-dicarboxylic anhydride condensed once with one nitrogen of ethylenediamine.

[discodermolide]

Remove all the solvent on the rotavap. Try dissolving it in hexamethyldisilazane, this will put TMS on the free nitrogen. Remove the HMDS on the rotavap. Then dissolve the residue in methanol, this will take off the N-TMS and give you back the free amine. Evaporate methanol to get, hopefully, the desired product.

[baum0372]

Thanks for the helpful suggestions everyone.

What I actually ended up doing was suspending the TFA salt in DCM, then adding Amberlyst-21 (slightly basic resin).  This clarified the solution within 2-3 minutes.  Then filtering off the amberlyst and evaporating gave my final product.  Whew! One more step to go.