[Honclbrif]

Hey Guys,

I've been trying to methylate my substrate* by pre-mixing it with methyl iodide in DCM, and slowly adding base at low temp. The problem is the deprotonated compound can go down an elimination pathway to form a better electrophile than MeI and I keep getting polymerized scum for my efforts. The same reaction conditions do work if I use something like acetic anhydride as the electrophile, so it is possible to modify this thing with electrophiles, but methylation has been a dud so far.

So my question is: Is it worth the risk to make some methyl trifluorosulfonate, or does someone have a sure-fire methylation protocol they always fall back on?

So far I've tried altering the base (the usual non-nucleophilic classics), the solvent, and the temp.

*It's the nitrogen in a rather crazy amide if you must know, and no, I can't start with it pre-methylated. I'd tell you more if I could. You know how it is...

[stewie griffin]

I think you can buy magic methyl. I really feel like a friend in grad school bought it and used it.
Another idea would be to see if you can do an Eshweiler-Clark (basically a reductive amination) http://en.wikipedia.org/wiki/Eschweiler%E2%80%93Clarke_reaction

[Dan]

Stewie, my first thought was some kind of reductive amination chemistry - but it's an amide, I don't think it will work.

Sigma (and no doubt many other suppliers) sell MeOTf. It's not very expensive, cheaper than Tf₂O.

[OC pro]

Magic methyl is actually methyl fluorosulfonate. Really really nasty stuff. Methyl trifluorosulfonate is a good alternative although from my eyes methyl iodide works better.
Have you thought using an excess of methyl iodide (I think of maybe 5 to 10equivalents)? Another base can also help. I mean switching the counterion. Don´t know which base you are using actually...