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Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: OrganicDan96 on July 24, 2019, 03:45:32 PM

Title: Deprotection of Boc in the presence of TBDPS
Post by: OrganicDan96 on July 24, 2019, 03:45:32 PM

I am designing a synthesis which is a variant of an existing synthesis with an important difference. so I need an alcohol protecting group that is stable to deprotection of Boc (TFA) and the deprotection of a benzyl group (H₂, Pd/C) so the best bet i could find is TBDPS which according to greens protecting groups is fairly stable to acid. so would TBDPS be stable to the deprotection of Boc?

any protecting group must come of in a very mild way with biproducts that are easy to separate.

Title: Re: Deprotection of Boc in the presence of TBDPS
Post by: rolnor on July 24, 2019, 06:03:42 PM

I think its OK if you monitor the reaction and neutralize as soon as the Boc is gone, with TFA this reaction is very fast.

Title: Re: Deprotection of Boc in the presence of TBDPS
Post by: wildfyr on July 24, 2019, 08:44:04 PM

Quote from: OrganicDan96 on July 24, 2019, 03:45:32 PM

any protecting group must come of in a very mild way with biproducts that are easy to separate.

So we all wish

Title: Re: Deprotection of Boc in the presence of TBDPS
Post by: rolnor on July 25, 2019, 06:59:09 AM

If you use TBAF to remove the silyl group the mixture becomes very basic, if you have problem with that you can use pyridine*HF but then you will have a little acidic conditions.

Title: Re: Deprotection of Boc in the presence of TBDPS
Post by: wildfyr on July 25, 2019, 09:06:59 AM

I think the silyl will come off in almost any fluoride conditions. Can likely use use MeCN and KF, which is about neutral.

Title: Re: Deprotection of Boc in the presence of TBDPS
Post by: rolnor on July 25, 2019, 10:05:03 AM

When you cleave the Si-OR bond with fluoride a RO- ion is created, this is basic. Normaly there is some water in TBAF so the RO- is protonated and OH- is formed. It is probably possible to have neutral conditions if a apropriate proton source is present.

Title: Re: Deprotection of Boc in the presence of TBDPS
Post by: OrganicDan96 on July 25, 2019, 01:41:09 PM

i think it will be ok, my molecule doesn't contain any particularly sensitive functional groups but it is right at the end of a long synthesis so material will be valuable.

Title: Re: Deprotection of Boc in the presence of TBDPS
Post by: wildfyr on July 25, 2019, 05:41:42 PM

What about KFHF then?

Title: Re: Deprotection of Boc in the presence of TBDPS
Post by: rolnor on July 25, 2019, 07:31:05 PM

Yes, I think that would work, maybe together with TBAF?