[russellm72]

Hi,

I wonder if anybody has experience of the methylation of a simple aliphatic acid chloride. I am currently trying the transformation using dimethyllithium cuprate but not with much success. Before anyone asks why you doing it this way, it is labelled in the carbonly and I have a supply of labelled acid chloride. It is also alpha halogenated so the conditions will clearly need to be mild. I recently saw a paper using grignards in the presence of iron salts and also have not tried dimethylcadmium yet which is reported to be good for such a transformation.

Any ideas from people with experience in this field appreciated.

Many Thanks

R.

[movies]

You might be able to do this with Pd as well.

Have you considered converting the acid chloride to the Weinreb amide and then adding a Grignard?  It might be a little tricky with the alpha-halogenation, however.

[russellm72]

No I hadn't thought of a Weinreb amide although it would add another step to the synthesis. I have never made one but guess the conditions could be found to react with the acid chloride. I remember reading they are quite stable so it may warrant purification of the intermediate before attacking with one eq of MeMgI at low temp.

Could be worth a stab.

Cheers