Good Morning,

Triethylamine is also a tertiary amine so it should be basic enough to deprotonate your compounds

In addition, it will not hydrolyze your ester on the time scale of a purification

However would extraction be efficient enough to obtain your compound pure enough ?

Side note, would it be possible to use sodium methoxide as the base?

Corentin Bon Thanks for your feedback. To answer your question, I plan on doing purification through flash chromatography, not extraction. The reason for needing to deprotonate is because in the current form the compound is insoluble in organic solvents.

DBU is quite basic (try acetonitrile as solvent) and non-nucleophilic

DBU looks like a good choice; TEA and DIPEA came to mind but their pKa is pretty similar to that of a tertiary amine so not knowing the pKa of your amine this would be a gamble. Methoxide will certainly grab your proton but is so strong it will also likely hydrolyze your ester. Good luck.

The solubility of your amine salt in a solvent is dependent on the counter ion. For example acetate salts have a different solubility profile than hydrochloride

salts which are useful for purifying amines on a gram or larger scale. If your salt is soluble in MeOH I would suggest using a strongly basic ion exchange resin column for neutralization which also avoids the problem of trans-esterification.

If your tertiary amine compound is in solid form, first purify your compound via crystalization instead of flash chromatography purification. Then your pure compound is quickly converted to basic form with concentrated sodium carbonate.But your tertiary amine compound that also has a methyl ester functional group is not stable. Your compound must be stored in the cold.

From 3o amine salt you can get free 3o amine by using aq. NaHCO3 . If you have no other water sensitive groups like acid chloride or anhydride or carboxylic acid (which can form soluble Na-salt of the free amine) functionality you can suspend (or make water solution ( the compound in ice water and treat it with requisite quantity of NaHCO3 (either solid NaHCO3 or saturated aqueos NaHCO3 solution can be used). CO2 gas will be evolved to set free the 3o amine. If the product ( free amino ester) is solid it will form ppt....just filter it , wash with little ice water and dry under vacum. If it is not solid or do not form ppt just extract it with some common organic solvents like diethyl ether, DCM, ethyl acetate or benzene.....wash the organic layer with water and collect the organic extract, dry it over anhyd. Na2SO4 . Removal of solvent (preferably under reduced pressure or with rotary evaporator) would furnish the amino ester. Ester groups (llike methyl, ethy or benzyl esters), amides, nitriles are not hydrolyzed by aq. NaHCO3 under this condition .

On many occasions I have prepared free methyl ester of amino acids from the respective hydrochloride salts methyl esters of amino ecis. ( even for one degree amine which are more unstable due to self condensation tendency to form lactam or amide I faced no problem. I hope for 3o amino ester it will be more easier).

In my opinion NaHCO3 washing is not enough, a quick comparison of pKas reveals that you need a stronger buffer. I think you can dissolve your salt in NaOH 1 M and then extract with organic solvents, that way you set your compound at pH 12.5-13.0, that seems suitable to get deprotonated amines.

Dissolve your salt in MeOH containing 1eq MeONa