Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: Reddart on July 02, 2015, 12:17:45 AM
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Any favorite deprotection conditions for a very hydrophobic product...it has long alkyl chains. I was thinking of trying TFA/a little water and THF ?
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You don't need to add water. TFA/DCM is a common prep.
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Thanks! Believe it or not, I have managed to go about 20 years in organic chemistry without ever using the Boc protecting group.
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Alcoholic HCl is good too. 1 M methanolic HCl at 50 °C takes off most Boc groups in a couple of hours.
I'm not a huge fan of TFA/DCM because you generally have to use it at high concentration (usually upwards of 25% v/v), so it's more hassle to quench than dilute HCl.
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But you can just vac it off! Methanolic HCl is good though, and easy to generate in situ with acetyl chloride so you can control the stoichiometry.
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Are there general principles one uses with respect to when to use a scavenger and which scavenger to use? Most of our work with BOC-protected amines does not involve obvious nucleophiles within the molecule being deprotected, but that may change.
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Are there general principles one uses with respect to when to use a scavenger and which scavenger to use? Most of our work with BOC-protected amines does not involve obvious nucleophiles within the molecule being deprotected, but that may change.
I like to use TFA/DCM (50/50) with triethylsilane as a scavenger as a general rule, even without obvious nucleophiles around. It all rotovaps off cleanly and usually gives reasonably pure substrate.
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Depending on the chemistry, I really like to dissolve the compound in minimal DCM and then add 4N HCl in dioxanes (Aldrich or others) and then let it stir a while and then blow N2 through the flask to purge the HCl. That generates the HCl salt nicely, which is often easier to carry forward than the TFA salt. But 50:50 TFA/DCM works well for more difficult to remove Boc groups as well as tBu esters. In many cases a scavenger is not needed, depends on the substrate. You can also make or buy 1-2N HCl in ether, but many compounds ppt from the ether solution before the Boc is fully removed, so you have to be careful that the reaction is complete then. I have recovered some materials from that system that still had 50% remaining as the Boc amine, as the material was so insoluble in ether.
One warning, if you use TFA, you will get the TFA salt, which can be bad if your next step include a amide or ester coupling, as you can often end up making the TFA amide as an impurity. I have seen that many times, it is hard to see on the NMR, as the TFA group is not visible in the Proton NMR. But it happens in some cases. HCl is better in those cases.
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I ended up using 40%TFA in DCM, removed the gross solvent on the rotovap, dissolved in hexane and washed with bicarb. I was hesitant to use HCl since I have an ester group on the molecule as well (but perhaps unfounded since there aren't any strong nucleophiles around).