[TheUnassuming]

I generally avoid DMSO for any strongly basic or acidic conditions because it can do some interesting/undesirable things that can be a little hard to predict.   

If your compounds are soluble in MeOH, my default methyl ester deprotection conditions are usually LiOH in MeOH/H2O (9:1).

I'm going to second the suggestion you got a while ago from guitarmaniac: try a lithium iodide/pyridine deprotection. 

[Dan]

For the N-Bn series, can you do the sequence with an ester that hydrolyses via the A_AL1 mechanism (e.g. t-Bu or PMB/DMB ester) and remove it with acid instead?

If you perform the sequence with RCO₂CH₂CH₂SPh, you can then deprotect in two steps:
1. oxidation to the sulfone with mCPBA, followed by
2. E1cb elimination of the carboxylate (i.e. forming vinyl phenyl sulfone) under mildly basic conditions (possibly during workup of step 1).

Both these approaches avoid relying on the very hindered acyl C as the reactive centre.

[orgopete]

The methyl and ethyl esters are both available? How is that possible or how were they synthesized?

[clemi2310]

Hello everyone! first of all thank you for all your answers.

I finally managed to get full conversion !!

I found a paper with conditions KOH with Toluene where they discuss about the role of KOH concentration, and it happens to work better when the aq KOH is not saturated but at weaker concentration.

So I decided to try  on the methyl ester NaOH 3M (instead of 10M) in THF/iPrOH at 120°C under microwave irradiation, but I was a bit absent minded and I put MeOH instead of iPrOH.

And I also increased the reaction molarity from 0,1M to 0,7M (better when it is more concentrated with microwaves)

After 4 hours 87% conversion and after 6 hours... full conversion ! I still want to optimize the reaction time with the temperature but it is much better!

I tried to do the same with iPrOH but it doesn't go to completion. It seems that methanol has a better role to play. Maybe solubility??


To answer your questions to get these esters I have three steps before. The starting material is either methyl or ethyl isonipecotate both available.