[ZidaneTribal]

I need the free base of L-histidine methyl ester dihydrochloride. I dissolved it in a saturated K2CO3 solution and extracted it with CH2Cl2, CHCl3 and EtOAc but no product was found in the organic phase. What am I doing wrong?

[AWK]

Try zinc dust in dry THF. After evaporation of THF solution dry ethyl ether may promote crystallization of ester from oil.

[wildfyr]

Even deprotonated it's still a pretty polar molecule. AWK I've never heard of such a trick, care to explain the mechanism?

[AWK]

Mechanism is very complicated:
Zn + 2HCl + ZnCl₂ + H₂
and needs 10 min. of reaction + filtration and evaporation (or direct using of the solution in the next reaction). Use eventually 2-3 times more THF than in procedure.
Ananda, K. & Suresh Babu, V.V. Deprotonation of hydrochloride salts of amino acid esters and peptide esters using commercial zinc dust. J. Peptide Res., 2001, 57, 223–226.

DOI:10.1111/j.1399-3011.2001.00790.x

[wildfyr]

I should have given this 4 seconds of thought before asking.

But still a clever way to do such a purification! This one definitely goes in the back pocket.

[AWK]

Too simple, do not take it into account. In the early seventies, we called it Fischer's method in the laboratory. Yesterday, I was surprised to see that it was published 30 years later.