[ringhio]

Hey can someone help me with this problem? I have an ethyl isoxazoline carboxylate and i can't convert it in the corrispondent acid with conventional hydrolysis, so i decided to use trimethyltin hydroxide. Today i run the reaction using 1 eq of ester and 1 eq of trimethyltin hydroxide, 80°C and DCE as solvent; i let stirring about 8 hours, but the reaction shows no good TLC, so i'm waiting for the NMR tomorrow. Do you think i should modify any parameters to make the reaction go? I'm not sure about the amount of the eq i have to use, because i couldn't find any informations in literature.

[pgk]

Structurally, isoxazoline ring is a cyclic alkylated oxime and therefore, it is expected to be stable under alkaline hydrolysis.
Hydrolytic Stability of Hydrazones and Oximes, Angewandte Chemie-International Edition, (2008), 47(39), 7523–7526
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743602/#SD1
So, why don’t you try to hydrolyse your ester under mild alkaline conditions?
A simple method for the alkaline hydrolysis of esters, Tetrahedron Letters, (2007), 48(46), 8230-8233
http://www.sciencedirect.com/science/article/pii/S0040403907018539

[ringhio]

Structurally, isoxazoline ring is a cyclic alkylated oxime and therefore, it is expected to be stable under alkaline hydrolysis.
Hydrolytic Stability of Hydrazones and Oximes, Angewandte Chemie-International Edition, (2008), 47(39), 7523–7526
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743602/#SD1
So, why don’t you try to hydrolyse your ester under mild alkaline conditions?
A simple method for the alkaline hydrolysis of esters, Tetrahedron Letters, (2007), 48(46), 8230-8233
http://www.sciencedirect.com/science/article/pii/S0040403907018539

Our isoxazoline has got an acid hydrogen, the one near the nitrogen and the carboxylate group, that's why we didn't try to hydrolyse it using alkaline conditions. 

[pgk]

What is the problem if you add the double amount of base (say KOH) and reflux in pure methanol (say 1-2h) and then, acidify after hydrolysis?

[Guitarmaniac86]

I used trimethyl tin hydroxide a lot during my PhD. 1 equiv will not cut it. Try 4 equivs. The most I had to use was 10 equivs of it.

I used the following paper:

A mild and selective method for the hydrolysis of esters with trimethyltin hydroxideNicolau et al  Angew. Chem. Int. Ed. 2005, 44, 1378 –1382

I have the pdf somewhere for the prep too.

[ringhio]

What is the problem if you add the double amount of base (say KOH) and reflux in pure methanol (say 1-2h) and then, acidify after hydrolysis?

i think the isoxazoline breaks up and rearranges into a lactone, but we definetely have to try it again

I used trimethyl tin hydroxide a lot during my PhD. 1 equiv will not cut it. Try 4 equivs. The most I had to use was 10 equivs of it.

I used the following paper:

A mild and selective method for the hydrolysis of esters with trimethyltin hydroxideNicolau et al  Angew. Chem. Int. Ed. 2005, 44, 1378 –1382

I have the pdf somewhere for the prep too.

thank you! that's the paper we used to do the first try. Now i'm trying again using another isoxazoline ring, this time more stable and maybe i can do both the KOH hydrolysis and trimethyltin hydroxide