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Topic: Removal of tetrabutylammonium impurities  (Read 15602 times)

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Offline reflux

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Removal of tetrabutylammonium impurities
« on: May 23, 2012, 11:57:33 AM »
What are the best ways to remove tetrabutylammonium impurities after a reaction with TBAF, TBAI, etc.  I have a polar amino acid compound which after purification by silica gel column (10% MeOH/DCM) or reverse-phase HPLC (30-70% MeCN/H2O + 0.1% NH4OH) still contains a lot of some tetrabutylammonium impurity (probably as the hydroxide).  It comes from a TBAF mediated OTBS deprotection that requires 3 eq of TBAF, which is why I get so much of the impurity.

Offline discodermolide

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Re: Removal of tetrabutylammonium impurities
« Reply #1 on: May 23, 2012, 01:49:50 PM »
What are the best ways to remove tetrabutylammonium impurities after a reaction with TBAF, TBAI, etc.  I have a polar amino acid compound which after purification by silica gel column (10% MeOH/DCM) or reverse-phase HPLC (30-70% MeCN/H2O + 0.1% NH4OH) still contains a lot of some tetrabutylammonium impurity (probably as the hydroxide).  It comes from a TBAF mediated OTBS deprotection that requires 3 eq of TBAF, which is why I get so much of the impurity.


Try an ion exchange resin?
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Offline nox

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Re: Removal of tetrabutylammonium impurities
« Reply #2 on: May 23, 2012, 09:14:09 PM »
Is your polar amino acid soluble in water? I used to have the same problem when working with unprotected sugars, always had a lot of tetrabutylammonium crap in my aqueous phase which I couldn't get rid of no matter how many organic washes I did.

One thing I found that worked really nicely is via anion exchange with potassium hexafluorophosphate (KPF6). After the reaction I just throw in 3 equivalents of KPF6, this makes a nice and greasy Bu4N+ -PF6 ion pair which dissolves very well in DCM. Wash the aqueous layer with DCM a few times and it cleanly removes all the tetrabutylammonium salts.

Offline Babcock_Hall

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Re: Removal of tetrabutylammonium impurities
« Reply #3 on: May 24, 2012, 06:51:19 PM »
Amino acids are eluted from Dowex 50 with ca. 3 M ammonia but a tetrabutylammonium ion should remain bound.

Offline g-bones

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Re: Removal of tetrabutylammonium impurities
« Reply #4 on: May 25, 2012, 07:15:43 PM »
maybe deprotect differently? 1% HCl in MeOH typically drops TBS groups like their hot.  MeOH is volatile and you can isolate the HCl salt of your amine.

Offline reflux

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Re: Removal of tetrabutylammonium impurities
« Reply #5 on: June 13, 2012, 11:31:39 AM »
Sorry for my late response.  These are all excellent suggestions.  I have a feeling many people dealing with this problem will benefit from this discussion.  I only have ~1-5 mg of material so I haven't been able to try these strategies myself, but I will once I have more in hand.

Thanks to all!

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