Chemistry Forums for Students > Organic Chemistry Forum for Graduate Students and Professionals

copper sulfate washes, lutidine, and DCM

<< < (2/4) > >>

Babcock_Hall:
We attempted to purify by means of a silica column but did not observe the desired product in any fractions.  My tentative conclusion is that we broke the glycosidic bond somehow.  We are very puzzled. Could prolonged exposure to the copper sulfate solution have this effect?
EDT
We rechecked the calculations for the synthesis, and there was more TBDMSOTf than we intended to add.  This might or might not have been the problem.

rolnor:
You could have hydrolysis of excess tbdmsotf on the column or in the workup, this make triflic acid so hydrolysis can be quick. You can add a little MeOH+TEA before workup, this will quench the reagent and keep pH high.
Edit: It is actually possible to break/activate glycosidic bonds with tbdsotf so this can be a concern. This is used in nucleoside synthesis, I have made that myself several times. So excess tbdsotf is no good and it could be a problem even if no excess is used.

phth:
Some suggestions:

Why not just add bicarb and extract with DCM (3 x) wash brine (optional), dry, conc. Should not be a problem with a good vacuum, and it is observable by TLC which may overlap with your product because lutidine moves in polar systems like MeOH/DCM.  Another way is to triturate with ethyl ether or hexanes to remove TBS junk and lutidine.

kriggy:
Could you use different base? I have good experience with DMF + imidazole as a system for OH silylations:

2-hydroxymethylaniline (123 mg, 1 mmol, 1 eq) was dissolved in dry DMF. Imidazole (163 mg, 2.5
mmol, 2.4 qe) was added followed by TBDPSCl (308 μL, 1.2 mmol, 1.2 eq). Reaction was stirred at
room temperature for 18 hours. Afterwards, water (20 mL) was added and the solution was extracted
with EtOAc (3x 20 mL). Organic extracts were combined and washed with sat. aq. NH4Cl (2x 20 mL)
and brine and dried with MgSO4 and evaporated to yield 270 mg of oil (75%)

Babcock_Hall:
IIUC lutidine, which is statically hindered, is more often used when there is a trifluoromethanesulfonate leaving group, whereas imidazole, which I believe is more nucleophilic, is used when chloride is the leaving group.  Let me make an educated guess:  Imidazole is a nucleophilic catalyst for TBDMS chloride.  However, one does not want imidazole to displace the trifluoromethanesulfonate group.

We had some problems with this reaction and purification again yesterday, which I may address on a companion thread (unless putting it into this thread would make it easier to follow).  For now, I will just note that after the copper sulfate wash, we had a product that was not homogeneous.  There appeared to be a light brown liquid, a whitish solid, and a purple solid.  Not all of this crude product came into our chromatographic solvent, which was 4% diethyl ether in hexanes.  Perhaps our wash left lutidinium trifluoromethanesulfonate with the organic, not the aqueous layer, and this was a part of the solid. 

I am reconsidering copper sulfate versus HCl washes.  IIRC someone thought that 1 M HCl was too strong for TBDMS groups.  What if we backed off the acid strength, either by going to 0.5 M HCl, or by using a weaker acid, such as KHSO4 or the sodium form?

Navigation

[0] Message Index

[#] Next page

[*] Previous page