[affa]

I am working to cleave the N-bound tert-butyl group from a tertiary amide (aliphatic one) to regenerate a N-H in secondary amide.

I have tried using trifluoroacetic acid (TFA) or even trifluoromethanesulfonic acid (TfOH) under refluxing dichloromethane conditions (~ 39 ^oC). However, the tert-butyl group is unreactive at all.

Can anyone suggest alternative conditions to deprotect a tert-butyl from amides? Thank for your attention.

[russellm72]

Can I ask why is it on there?

R.

[affa]

tert-butyl tertiary amide was prepared to control the amide rotamer by forcing another alkyl substituent (reaction site) "anti-" to the amide carbonyl. Otherwise, the alkyl substituent would be "syn-" to the amide carbonyl, which cannot lead to desired reactions.

Do you have any idea to cleave this bulky group?

[agrobert]

Can you expose your compound to aqueous acidic conditions?

[affa]

coz I think protic acid in non-aqueous medium is more "acidic" than that in aqueous, where the acid protons mostly occupied by aqueous but not to protonate the amide substrates.