[Ingeniosuccinimide]

Hello,

I need and advice: what could be (a) good method(s) to methylate sulfur in cysteine (to get S-Methyl-cysteine)?

[Hunter2]

Probably Methylgrignad. CH₃MgI

Or Methylchloride/bromide  in alcaline solution

http://www.google.com/patents/US3905973

http://www.google.com/patents/US3897429

[Babcock_Hall]

Why not just buy it?  If you have to make it, you may want to protect the nitrogen atom.

[sjb]

Probably Methylgrignad. CH₃MgI

Or Methylchloride/bromide  in alcaline solution

http://www.google.com/patents/US3905973

http://www.google.com/patents/US3897429

Could you really use both? The polarity of the synthon is not the same in either case.

[Ingeniosuccinimide]

Why not just buy it?  If you have to make it, you may want to protect the nitrogen atom.

The price is an issue, when you compare prices for sellers available where I work, there is a very notable difference in prices between these two.

By the way, my plan is to protect the nitrogen afterwards, so that would be good.

I'm only not sure if methyl halogenide approach to thiole methylation is promising since I didn't find any example..

Any other suggestions?

[Hunter2]

Maybe easier to at CH₃-S^- to  3-Bromine-alanine. Br-CH₂Ch(NH₂)-COOH

[Babcock_Hall]

Hunter,

How would you control the stereochemistry of carbon-2?

[clarkstill]

Maybe easier to at CH₃-S^- to  3-Bromine-alanine. Br-CH₂Ch(NH₂)-COOH

This seems like a very bad idea...

1. I don't think it would be particularly easy to brominate alanine, so not sure where the SM would come from
2. It would probably form an aziridine if the amine wasn't protected (and possibly even if it was, i've had NHBoc trap onto adjacent leaving groups)
3. The bromide would probably leave in an E1cb if you exposed it to base

I think methyl iodide+cysteine sounds much easier. You might even get away with not protecting the nitrogen, sulfur is a much better nucleophile. I found many examples, e.g. JOC 1985, 1264, or if you dont have access, Beilstein J. Org Chem 2012, 1105 (open-access).