[OrganicDan96]

I am protesting a secondary amine with Fmoc-Cl, i had it stirring with DCM in the presence of potassium carbonate over night as it said but this morning the TLC showed no product, it should be done by now. what is going wrong and how could I get this to work? i have left it over the weekend but if nothing happens by Monday I will have to recover my starting material.

[wildfyr]

Did you dry the potassium carbonate? If it was just sitting around in an opened bottle it probably has significant water content.

A solid bake in a vacuum overnight at 150°C+ should do the trick. Store it in a desiccator.

[OrganicDan96]

Did you dry the potassium carbonate? If it was just sitting around in an opened bottle it probably has significant water content.

A solid bake in a vacuum overnight at 150°C+ should do the trick. Store it in a desiccator.

didn't do anything special but it said it was anhydrous, also i dried the DCM

[wildfyr]

If the seal was previously opened then it probably wasn't very anhydrous anymore. Drying that salt is so simple, I do it to a big batch and just put it in the desiccator and use for a long time for everything.

[OrganicDan96]

i'm not overly convinced that this was the problem because TLC showed a very bright spot that corresponds to Fmoc-Cl so there definitely is some in there.

[wildfyr]

Hmm... I'm surprised that chloroformate can survive on a TLC plate. Are you sure that's not hydrolsis product? (carboxylate? alcohol?)

[OrganicDan96]

Hmm... I'm surprised that chloroformate can survive on a TLC plate. Are you sure that's not hydrolsis product? (carboxylate? alcohol?)

its possible, the spot was very clean and round and quite high up on the plate, i would expect the alcohol or carboxylate to have quite a low Rf value in 4:1 hexane ethyl-acetate.

[wildfyr]

I think the alcohol would run pretty well, Fmoc is rather greasy. I think I. Hydrolyzes into the alcohol and eliminates Co2

[OrganicDan96]

I think the alcohol would run pretty well, Fmoc is rather greasy. I think I. Hydrolyzes into the alcohol and eliminates Co2

could it be possible that my product is under the alcohol spot and the reaction is working but not complete?

[wildfyr]

Unlikely but you could run the column and take nmr.

[kriggy]

I never had succes with carbonates during acylation reactions. Try triethylamine instead

[OrganicDan96]

I never had succes with carbonates during acylation reactions. Try triethylamine instead

that would deprotect the Fmoc protected amine at the end of the reaction wouldn't it?

[wildfyr]

I don't understand your last response. There are two amines in our discussion. TEA won't react, it's tertiary...

[OrganicDan96]

I don't understand your last response. There are two amines in our discussion. TEA won't react, it's tertiary...

Fmoc protected amines can be deprotected by amine bases the common conditions are 20% piperidine in DMF i just thought TEA would do the same

[wildfyr]

Piperidine and TEA are quite different. Cyclic secondary amines are rather strong nucleophiles and bases. Also, you use 1.1 equivalents TEA, not the huge over equivalency of the piperidine deprotection.