I am performing a Boc-deprotection with HCl in organic solvent (dioxane or Ethylacetate) but would like to isolate the free amine.
Several problems:
- Neutralizing with inorganic base as NEt3 involves too large amounts as I am using 25 eq of HCl (reaction is too long with less eq)
- Washings with carbonate solution leads to product degradation
Has someone experience of such situation ? Could ion-exchange resins help ? Which one ?
The process has moreover to be upscalable ...
Thanks in advance
Mixture neutralization after Boc- deprotection , you need to neutralize by sodium bicarbonate to get fee amine otherwise it will be water soluble hydrochloride
Is it anhydrous H Cl? You can remove with vacuum and dry ice trap.
but I recommend you switch to Nafion. Very strong acid - and you remove by Filtration!
Article Polymer-supported acidolysis of protecting groups used in th...
It all depends on the character of your molecule and its solubility on organic but in most situations, I would try to evaporate dioxane and excess of HCl. Then the crude dissolved in saturated sodium bicarbonate, then extract the free amine with CH2Cl2. Combine all DCM extracts, wash it with brine, dry with MgSO4, and evaporate.
If free amine is not soluble with DCM or AcOEt, or the rest of the molecule is sensible to the NaHCO3 then this method is not suitable and I would think about carrying on with the protonated amine in followed reaction (deprotonated in situ with some organic base like NEt3 if necessary).
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