[FTO]

I'm doing several amide coupling reactions using acid chloride and TEA. The product looks pure on NMR, HOWEVER there is HUGH amount of TEA, even more than my desired cmpd.

I've done columns with various gradients(DCM/MeOH only, it won't resolve in EtOAc), my cmpd came out clean (from other impurities). But on TLC (after column) my "clean" cmpd always has TEA, although the separation is very good, suggesting TEA shouldn't have come out with my cmpd.

I tried to protonate TEA using 1M HCl, and wash it off. the result was that i was losing 70-80% of my cmpd in aq. layer. The stuff I was making also has tertiary amine motif, I suppose whatever works for YRA would also work for my cmpd.

Tried to vac TEA off on a high vac at 45C for 3 hrs, nothing happened to TEA.

Also tried to pull TEA off by washing with Et2O in a little bit of DCM (10x plus) the results were disappointing.

I've tried any and everything I can think of/in the book, still in misery. Any expert advice is much much appreciated!!!!

[opsomath]

What should work, and that you can try:

- High vac overnight
- Dissolve / suspend in toluene and rotovap off (azeotropic forcing)
- Repeated washing with neutral water (TEA is 20 g/mL soluble)
- Vacuum distillation

Your TEA is probably in the acid chloride form still if it's not coming off with these normal things. Try washing with basic aqueous solution then any of the above things.

[discodermolide]

What molar ratios are you using?

[Borek]

To avoid ambiguity: what is TEA? Wiki suggests three possibilities.

[FTO]

What should work, and that you can try:

- High vac overnight
- Dissolve / suspend in toluene and rotovap off (azeotropic forcing)
- Repeated washing with neutral water (TEA is 20 g/mL soluble)
- Vacuum distillation

Your TEA is probably in the acid chloride form still if it's not coming off with these normal things. Try washing with basic aqueous solution then any of the above things.

-tried high vac overnight, over weekend actually, didn't work.
-I've got a tertiary amine motif on my cmpd, so water is probably not a good idea (I've been losing yield doing aq workup)

I'm going to try toluene, sounds like a possible solution, probably need several washes.

[FTO]

What molar ratios are you using?

I'm using 1.2 eq of TEA

[FTO]

TEA = triethylamine

[Babcock_Hall]

Does your compound have a free carboxylic acid function or something similar?

[FTO]

No, it is amide coupling. So start material does, not the product.

[orgopete]

I tried to protonate TEA using 1M HCl, and wash it off. the result was that i was losing 70-80% of my cmpd in aq. layer. The stuff I was making also has tertiary amine motif, I suppose whatever works for YRA would also work for my cmpd.

If I understand this, you have two amines with similar basicities and tried to wash out one of them by adding acid. Was this a titration? If you take a small sample and add some HCl (solution still basic), is your sample in the neutral and aqueous layers? If it is, then based upon what you have said, I suggest using an ion exchange column. Charge your compound onto a sulfonic acid ion exchange column and begin washing with ammonia (a base). The weakest base will be exchanged first. As the fractions elute, the strongest base should be eluted last. You can look this up to see how it is done. As I recall, this is how amino acids can be separated.