Diphenyl ether formation

[Rebeka]

Hello everyone! I was wondering if anyone could help me with a functional group formation and curly arrow mechanism. On the drug Ibrutinib there is what I think is a diphenyl ether. I know that the Williamson Synthesis can be used to form ether but I do not understand how to form a diphenyl ether at all. I tried looking up the Ullmann synthesis but I am not sure if that would be the correct way to form a diphenyl ether. Could anyone please show me how/ what reaction would occur that would form a diphenyl ether on Ibrutinib? Any help or suggestions would be very much appreciated. Thank you!

http://www.chemspider.com/Chemical-Structure.26637187.html 

I have attached an image of Ibrutinib in the URL above 

[BabcockHall]

My understanding of the Ullmann reaction is limited, but it appears to be a way to make biaryl compounds.  Relative to what you want, the product is missing the oxygen.  Can you explain why you think that the Williamson synthesis might not work in this instance?

[Rebeka]

I have been told the Williamson synthesis would not work to form the ether I need because diphenyl ether is an aryl halogen. Beyond that my understanding of why it will not work its very limited. I know you can form an ether from a benzene ring, but I do not understand how to form an ether with two phenyl/aryl groups as the R groups. Does anyone know the reaction mechanism that I would use to form the ether on Ibrutinib? 

https://www.youtube.com/watch?v=CnZQiHgnuok

I tried using this as a template for the reaction, but I'm honestly not sure if I'm on the right path here 

[hypervalent_iodine]

Are you actually trying to make this?

[Rebeka]

No, it is just for a project to show a possible reaction mechanism to form it. 

 

[hypervalent_iodine]

There are a few ways. Ullman, as you suggested, Buchwald Hartwig coupling, or Chan Lam. 

Organic portal has an overview of these, plus literature examples. https://www.organic-chemistry.org/synthesis/C1O/biarylethers.shtm

[BabcockHall]

@OP, The Williamson ether synthesis is usually given as an example of S_N2 chemistry in introductory organic chemistry.  Aryl bromides or aryl iodides are unreactive in S_N2 reactions.  Why do you suppose that is the case?