[chysce]

Greetings :]

I'm having trouble debenzylating the following amide:  https://imgur.com/C91sDqJ

What I have tried so far:

H2, 1atm, Pd/C in MeOH  ---> starting compound isolated only
H2, 1atm, Pd/C in AcOH ---> had a new TLC spot, left it to react a couple of days more, after which the TLC plate was a complete mess (I did heat the reaction mixture upon evaporation of solvent though)

HCOONH4, Pd/C in MeOH reflux  ---> starting compound isolated only
HCOONH4, Pd/C in iPrOH in microwave 600W 10 minutes  ---> starting compound isolated only

aqueous HBr overnight ---> nothing
HCOOH at 60 oC for 3h... ---> formyl ester isolated only

I have once again set up a reaction in AcOH with H2, because that was the only one giving the slightest hint of the product. I'll be monitoring reaction closely and will take care when rotavaping the mixture afterwards.

Other options are Li or Na in liquid ammonia and I'm reluctant to try that honestly.
As for hydrogenolysis I am worrying that increased pressure might result in pyrrole being reduced as well.
Would Pd(OH)2 help?

Any help would be much appreciated

[sjb]

What's your next step or two? Might the alcohol be interfering?

[chysce]

Deprotection is basically the last step.
Ill be sending the product for some biological evaluation and will likely be making several esters of the alcohol for the same purpose.

[Babcock_Hall]

What if you esterified the alcohol first, then debenzylated? 

[wildfyr]

Isn't the ester going to be destroyed during such a reduction? Especially in methanol or acetic acid...

[crawlingmcedge]

If you have the money to spare, you can try changing from Pd/C to more exotic catalysts.

I've heard good things about Pd(0) encat from Sigma.

[pgk]

What you want is the hydrogenolysis of a benzylamide that is not so easy, such as a benzylamine.
However, benzylamides can easily be deprotected under mild oxidative conditions but you need to protect the alcohol group first:
Oxidative Debenzylation of N-Benzyl Amides and O-Benzyl Ethers Using Alkali Metal Bromide, Organic Letters, (2014), 16(14), 3812–3815
https://pubs.acs.org/doi/abs/10.1021/ol501703y
Oxone® is potassium peroxymonosulfate (KHSO5).

[chysce]

@pgk

Yeah, I've seen that paper. I will most likely try several reactions on a precursor which doesn't have alcohol.
Might as well try that reaction.

I'll keep you guys posted

[TheUnassuming]

Amide debenzylation can be very rough in my experience, so if possible I would highly suggest using a different protecting group.  Especially since you have essentially a hemiaminal which will almost certainly give you troubles when you hammer it to get the benzyl off.

If that's not possible, I'd add these into your que for debenzylation conditions:
1) add an equiv or two of 1M HCl to your standard MeOH conditions
2) switch Pd/C for pearlman's catalyst with your standard MeOH conditions 
3) run several of your conditions listed as N/R in a bomb with escalating pressure if there is no reaction. 

The last time I did a debenzylation of an amide it took ~80psi H2 with a little bit of acid for a day or two to get it to come off all the way.

Good luck!