[kriggy]

Oh, I didnt thought of that.. but piperidine is nucleophilic, TEA is not. You could try pyridine as well

[OrganicDan96]

Oh, I didnt thought of that.. but piperidine is nucleophilic, TEA is not. You could try pyridine as well

Yeah pyridine might be good because it's pKa is lower than that of TEA

[wildfyr]

Pyridine is a better nucleophile I believe.

[Doc Oc]

Tertiary amines shouldn't be too dangerous to Fmoc groups, as others have noted.

The method I've used to protect amines is to make a 1:1 mixture of THF/1M NaHCO3. The Fmoc survives this condition and if your product doesn't just precipitate out you can rotovap the organic off and then do an extraction with ether or ethyl acetate.

[OrganicDan96]

Tertiary amines shouldn't be too dangerous to Fmoc groups, as others have noted.

The method I've used to protect amines is to make a 1:1 mixture of THF/1M NaHCO3. The Fmoc survives this condition and if your product doesn't just precipitate out you can rotovap the organic off and then do an extraction with ether or ethyl acetate.

My supervisor has told me not to use triethylamine as he thinks it would just deprotect the product. We have a THF still in the lab so i can gen dry THF easily. I have also put some potassium carbonate in the oven to dry like others noted. I i will take more care with dry conditions next time.

[Babcock_Hall]

I have not reviewed the FMOC deprotection literature, but diisopropylethylamine is even less nucleophilic than TEA is, unless I am mistaken.

[clarkstill]

You could try grinding the K2CO3 in a pestle and mortar. In my experience this leads to MUCH higher rates than the more coarse granules out of the pot.

Also, have you tried biphasic conditions? A typically way to put a carbamate on amines is to stir with the chloroformate and aqueous K2CO3. It's always surprised me that the chloroformates don't rapidly hydrolyse under these conditions, but it works. The carbonate is only there to mop up the HCl you form in the reaction (a la Schotten-Baumann).

Is there any other reason the reaction might be slow? Hindered amine? Is the amine SM a salt, and if so are you adding an extra eq. of base?

[wildfyr]

On water reactions are fascinating, there are some that seem preposterous that they work.

Here's a great example: the way you make benzoyl peroxide on the bench scale is by adding benzoyl chloride to 30% aqueous H₂O₂ with NaOH. On its face this should produce benzoic acid or at best benzoyl hydroperoxide, but instead you get a 50+% yield of benzoyl peroxide.

In a similar vein, here is aryl lithium chemistry done in air in glycerol http://onlinelibrary.wiley.com/doi/10.1002/chem.201705577/abstract

Interface chemistry is a tremendous untapped resource beyond just emulsion polymerizations.

[Doc Oc]

My supervisor has told me not to use triethylamine as he thinks it would just deprotect the product. We have a THF still in the lab so i can gen dry THF easily. I have also put some potassium carbonate in the oven to dry like others noted. I i will take more care with dry conditions next time.

I've not had a huge problem with tertiary amines removing Fmoc, but since I use a totally different method to do the protection I won't try to convince you.

As I said earlier, I do this reaction regularly with water as the solvent, so I don't know that keeping things rigorously dry is necessary.

[OrganicDan96]

I have not reviewed the FMOC deprotection literature, but diisopropylethylamine is even less nucleophilic than TEA is, unless I am mistaken.

I could try that

Is there any other reason the reaction might be slow? Hindered amine? Is the amine SM a salt, and if so are you adding an extra eq. of base?

it is a bit hindered but not overly hindered, the procedure i am followed (not a literature procedure) worked over night with exactly the same substrate so i don't know why it didn't work (or was just too slow)

[crawlingmcedge]

TEA will certainly start to deprotect Fmoc. Avoid using it.