[lancenti]

Hi guys.

I was doing a Cbz protection for D-Valine and I'm having some problems removing the 1,4-dioxane. Thus far I've washed with water, subjected to rotary evaporation (down to about 10 mbar, 40 oC water bath), and high vacuum but it seems that it's sticking to the Valine like glue.

I'm currently considering using a silica plug to try to wash out the 1,4-dioxane, but I was wondering if there was another way since I suspect that I'll lose quite a bit of compound to the column if I do this.

[OC pro]

I doubt that you have problems in removal of dioxane via rotary evaporation. However, it is easily removed via freeze drying.
Have you considered your product to be a sticky oil and not a solid?

[Dan]

I've never had problems removing dioxane with a rotavap, maybe just leave it for longer under vacuum if you don't have a freeze drier?

You could triturate the dioxane out (or precipitate out the Z-Val-OH) with a suitable organic solvent, perhaps hexane?

I wouldn't fancy running this through silica either. Will the presence of dioxane affect the next step?

[lancenti]

Thanks for the replies!

It's stuck as a sticky oil, and NMR clearly shows the dioxane peak. Left it under vacuum overnight, still the same.

I guess I can put it through to the next step since it's just activation with CDI.

[OC pro]

Yeah you can directly use it. Have you calculated the amount of dioxane present in your product? Be aware that the dioxane peak represents 8H so even with less than 1-2 weight% content in your product you will clearly see the dioxane peak. You should look at the NMR spectra more thoroughly. Every information has to be verified.
So as suggested before, your Cbz protected valine is an oil (just from my experience).

[jlawrence]

quite easy actually, I think. Add several drops of CHCl3 until the whole product dissolves, and evaporate it by vacuum (schlenk line), repeat it one more time and most likely the dioxane will be gone