[reflux]

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.

[discodermolide]

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?

[nox]

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.

[Babcock_Hall]

Amino acids are eluted from Dowex 50 with ca. 3 M ammonia but a tetrabutylammonium ion should remain bound.

[g-bones]

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.

[reflux]

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!