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Hydrolysis of Esters with Trimethyltin Hydroxide

Daniel Walton  Follow
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?

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Dan Gall  Follow
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

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Dave Walter  Follow
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.

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Chuck Smallman  Follow
Quote from:
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. 

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Christopher Patterson  Follow
Quote from:
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

Quote from:
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

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