[watizit97]

Hi. I am currently doing a research project on synthesizing a water-soluble rotaxane via Diels-Alders reaction. But I am facing a problem in synthesizing this molecule(please refer to attached photo) which is part of the process to synthesize a dienophile for Diels-Alder reaction. I anticipated to be able to synthesize compound 17 from compound 16 via hydrolysis of the methoxycarbonyl group, but it went unsuccessful. I think instead of the methoxycarbonyl group, the maleimide group underwent hydrolysis. Are there any ways to resolve this issue? How can I undergo hydrolysis on the -COOMe group without affecting the maleimide group?

[rolnor]

You can not hydrolyze the ester with methoxide, you need hydroxide.

[AlphaScent]

As rolnor said you need hydroxide to hydrolyze esters.  I would think if you used a stoichiometric amount of hydroxide the methyl ester would react much more readily than the maleimide.  This reminds me of Gabriel and you really have to pound it to hydrolyze to the primary amine. 

Is this theoretical or are you actually doing this synthesis?

[kriggy]

I hydrolyzed methylesters with K2CO3 in MeOH/water even at room temperature. Might be even more mild than 1eq of hydroxide

[watizit97]

As rolnor said you need hydroxide to hydrolyze esters.  I would think if you used a stoichiometric amount of hydroxide the methyl ester would react much more readily than the maleimide.  This reminds me of Gabriel and you really have to pound it to hydrolyze to the primary amine. 

Is this theoretical or are you actually doing this synthesis?

I see, thank you! I’ll consult my supervisor whether or not he agrees to this idea. And, I am actually synthesizing this molecule for my college research project.

[watizit97]

I hydrolyzed methylesters with K2CO3 in MeOH/water even at room temperature. Might be even more mild than 1eq of hydroxide

Could you share a reference to that statement?

[rolnor]

I wonder, with the K2CO3 system, was this a aromatic acid methylester or a aliphatic one? The aliphatic is much easier to hydrolyze.

[kriggy]

I hydrolyzed methylesters with K2CO3 in MeOH/water even at room temperature. Might be even more mild than 1eq of hydroxide

Could you share a reference to that statement?

I dont have a reference, its just something I tried and it worked. It is probably not general method but it worked for me. In the end I used hydroxide anyway but for different reasons.

@rolnor: its was aromatic