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Specialty Chemistry Forums => Biochemistry and Chemical Biology Forum => Topic started by: whiteblankpage2011 on August 12, 2014, 09:02:26 PM

Title: Fmoc deprotection
Post by: whiteblankpage2011 on August 12, 2014, 09:02:26 PM

Hello,

I'm trying to do a fmoc deprotection of a fmoc-4-amino-cinnamic acid (p-ACA)
After attaching the protected p-ACA to a bead and acetylating any beads that didn't react, the next step is to deprotect the p-ACA.
There are three methods I can use:
1. 20% piperidine/DMF solution for 10-30min (slow shaking)
2. 50% triethylamine/DCM solution for 18h (slow shaking)
3. 50% diethylamine/DCM solution for 3h (slow shaking)

Since the piperidine I ordered hasn't arrived yet, I'm using method #3.
However, when I make the 50% diethylamine/DCM solution, a precipitate forms. Does anyone knows what the precipitate is? Any side reactions? Can the precipitate interfere with the deprotection rxn I wanna perform?

Thank you,

Title: Re: Fmoc deprotection
Post by: clarkstill on August 13, 2014, 04:05:14 AM

I guess it could be doing SN2 with dichloromethane and forming the corresponding tertiary amine HCl salt, or quaternary ammonium salts.  It's a very slow reaction though... how quickly did the precipitate form? Any chance your DCM is contaminated with something, e.g. some acid?

I've done the same deprotection in neat diethylamine before, so that might be a way of avoiding the problem. That wasn't in solid phase though, so not sure whether it'll swell the beads properly.

Title: Re: Fmoc deprotection
Post by: whiteblankpage2011 on August 13, 2014, 12:40:13 PM

Quote from: clarkstill on August 13, 2014, 04:05:14 AM

I guess it could be doing SN2 with dichloromethane and forming the corresponding tertiary amine HCl salt, or quaternary ammonium salts.  It's a very slow reaction though... how quickly did the precipitate form? Any chance your DCM is contaminated with something, e.g. some acid?

I've done the same deprotection in neat diethylamine before, so that might be a way of avoiding the problem. That wasn't in solid phase though, so not sure whether it'll swell the beads properly.

The DCM is in a sure seal bottle. I don't believe I contaminated it, since I always use a clean non-coring needle when I need to extract DCM from the bottle.
The precipitate formed after one day. So I guess I can't make that stock ahead of time.