[zarhym]

Greetings,

This proposed reaction seems very risky to me. From my understanding, benzyl-o deprotection is strong enough to hydrogenate halogens. Especially, this chloride atom very reactive since its on benzyl position with two strong fluoride atoms attached to the same benzyl position.

I searched in reaxys, I can not find a single record that the benzyl-o group can be deprotected with benzyl chloride existed on the molecule.

If the Pd/C hydrogenation does not work (very likely), I believe that my best chance is either change the protection group (meaning start over the whole synthesis) or oxidize this molecule into benzoic ester then hydrolysis.

So far, I cannot convince my boss this is not a feasible route since there is little information I can find.
Do you have any suggestions?

Thanks a lot.

Zarhym

[pgk]

Benzyl ethers are easily hydogenalyzed with Pd/C in ethanol at 25oC, while alkyl halides need higher temperatures (e.g. 50oC) together with an additional source of hydrogen such as formate or bicarbonate salt, due to the catalyst poisoning. On the other hand the meta-substitution helps the hydrogenolysis of alkyl halides by deactivation of the meta- aromatic carbon.
See also:
http://www.chemicalforums.com/index.php?topic=81020.0
Thus, selective benzyl deprotection can be achieved with a little more of Pd/C catalyst in ethanol at 20oC and using the stoichiometric amount of hydrogen gas, as triturated by the gas trituration burette.
Do not add acetic of formic acid as an hydrogenation accelerator.
(Hint: Reaxys is a useful and powerful tool but it cannot cover all existing or hypothetical pathways of Organic Synthesis.)

[zarhym]

Benzyl ethers are easily hydogenalyzed with Pd/C in ethanol at 25oC, while alkyl halides need higher temperatures (e.g. 50oC) together with an additional source of hydrogen such as formate or bicarbonate salt, due to the catalyst poisoning. On the other hand the meta-substitution helps the hydrogenolysis of alkyl halides by deactivation of the meta- aromatic carbon.
See also:
http://www.chemicalforums.com/index.php?topic=81020.0
Thus, selective benzyl deprotection can be achieved with a little more of Pd/C catalyst in ethanol at 20oC and using the stoichiometric amount of hydrogen gas, as triturated by the gas trituration burette.
Do not add acetic of formic acid as an hydrogenation accelerator.
(Hint: Reaxys is a useful and powerful tool but it cannot cover all existing or hypothetical pathways of Organic Synthesis.)

Thanks a lot.
I'll give it a try and let you know what happens.

[pgk]

You are welcome.
If you use the balloon-injection-seal technique:
1). Add a slight excess of hydrogen, in order to offset the gas diffusion through the balloon’s wall, during the hydrogenation (hydrogen is the smallest molecule and can freely pass through polymers).
2). Press tightly the balloon before filling with hydrogen, in order to be sure that there is no air left, therein.
Good luck.

[Doc Oc]

If you have trouble with hydrogenolysis of the benzyl group, try TBAF. I've removed both benzyl esters and Cbz protecting groups by stirring in 1M TBAF in THF.

[rolnor]

Trimethylsilyliodide would probably work fine.

[rolnor]

TBAF is basic and containes water, this could cleave esters and carbamates but I doubt it could cleave ethers?