I have synthesized the molecule below possessing a doubly, boc protected heterocyclic amine and a terminal alkyne.

Upon attempting a TFA/$\ce{CH2Cl2}$ Boc deprotection I believe my alkyne is being hydrolysed.

1.) I wish to use TMSI to perform the boc deprotection but cannot find information on how it acts in the presence of alkynes. Would TMSI iodinate, silylate or otherwise interact with the alkyne?

2.) Is there any way to make use of TFA/$\ce{CH2Cl2}$ and prevent the alkyne hydrolysis?

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  • $\begingroup$ Can you use HCl/Dioxane? $\endgroup$ – Waylander Mar 10 '17 at 22:19
  • $\begingroup$ @Waylander why do you think this would help? Also, I imagine the hydrolysis is because of the presence of water? Is this theory correct? $\endgroup$ – Hazinga Mar 10 '17 at 22:21
  • $\begingroup$ HCl/Dioxane is a method we use extensively for removing BOC groups. Vac down hard to remove xs HCl before adding water should prevent any hydrolysis, indeed you may not need aq workup. How are you working up the TFA deprotection? $\endgroup$ – Waylander Mar 10 '17 at 22:25
  • $\begingroup$ Have you tried just heating it? One of my colleagues had really good luck with simple thermolysis. I would think that the first Boc will fall off easily at least. $\endgroup$ – jerepierre Mar 10 '17 at 22:27
  • $\begingroup$ The first BOC should come off with nucleophiles eg MeO-. What concentration of TFA are you using? $\endgroup$ – Waylander Mar 10 '17 at 22:28

TMSI was used successfully without damaging the alkyne as per this protocol.



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