I trying a reaction to protect 5'-OH of a modified nucleoside with DMT-Cl and DIPEA in pyridine. I have used 2 eq of DMT-Cl for 24 hour at room temperature. But the reaction is still incomplete. I have found a lot of starting material unreacted after monitoring by TLC. How can I reach the completion of this reaction?
Nurul，did you check was there any DMT-Cl left? How did you dry your SM before reaction?
You may try to check purity of both reactants using TLC, comparing melting point with literature value.
Try to increase the stirring of the reaction medium.
I suggest this webpage, which might be helpful to you
http://www.chem.rochester.edu/notvoodoo/pages/how_to.php?page=improve_yield
Checking whether any DMT-Cl is left in the reaction mixture is a good advice. Typically, because DMT-Cl is a bulky reagent, the reaction is supposed to be selective to 5'-OH position; however since we don't know the exact structure of the substrate, chances are that DMT-Cl may potentially react with some other part of the molecule (if the base contains active amino group, for example).
Also, I would make sure that the reaction media is anhydrous.
Finally, you can try adding catalytic amount of DMAP; in this case though, I will consider a stronger base like Et3N or Hunig base (otherwise DMAP will be protonated since it is much more basic than pyridine).
Good luck !
If you used the ratio of DMT-Cl to your nucleoside as 1.05:1, and your nucleoside possessed a primary 5'-OH, the reaction would be over in 2 h. As it is not the case, there are two options: 1. the moisture is present in the reaction mixture and 2. your DMT-Cl is contaminated with DMT-OH. To repeat this synthesis successfully, you can begin with drying the nucleoside by triple co-evaporation with anhydrous pyridine. The reaction then can be carried out by stirring the suspension of the nucleoside in anhydrous pyridine with 1.05 equiv. of DMT-Cl. No additional catalysis is required or recommended. TLC analysis is best done in MeOH-DCM 1:9 or 1:19. If the reaction does not work under the anhydrous conditions or furnishes an isolated yield of
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