[Shadow]

How to synthesize the molecule below? I attached my attempt (the methylcyclopropane could be deprotonated with BuLi), but I am not sure how to do the chlorination.

[kriggy]

Would it be possible to run chlormethylation reaction on N,N,N'-Trimethyl-methanediamine?

[AWK]

What about of commercial 2-cyclopropylethanol as starting material?

[Shadow]

Would it be possible to run chlormethylation reaction on N,N,N'-Trimethyl-methanediamine?

It would destroy the aminal, wouldn't it?

What about of commercial 2-cyclopropylethanol as starting material?

Okay, it can be tosylated and reacted with methylamine, and the product reacted with formaldehyde and dimethylamine (hoping that the cross-condensation product would have the highest yield). Any better suggestion?

[beardy]

[beardy]

Just realized reductive amination works with aldehydes and ketones. Idk about amides.

[kriggy]

Im running an amination of amide and its not working that well. It should form 6-membered cycle and I got about 30% yield after 24h reflux in 10%HCl. With about 30% of starting material didnt react. Im not sure if it could work in aliphatic series

[Shadow]

Would this actually work:  2-cyclopropylethanol can be tosylated and reacted with methylamine, and the product reacted with formaldehyde and dimethylamine (hoping that the cross-condensation product would have a nice yield).

[kriggy]

You could also try mitsunobu reaction, it could save you one step

[Shadow]

Nice one.

[Dan]

You could also try mitsunobu reaction, it could save you one step

I don't think a Mitsunobu will work with methylamine - you need a nucleophile with a pKa < 15, you can use HN₃ or phthalimide, but you're still going to have to deprotect and alkylate.

Monoalkylation of methylamine by S_N2 (with n alkyl (pseudo)halide) is potentially problematic anyway.

A mixed condensation of the two amines with formaldehyde will probably give a statistical mixture, but this is not really a problem if you use a large excess of formaldehyde and dimethylamine (this would generate a lot of the unwanted tetramethyl aminal as a waste byproduct).

I wonder if it would be easier to make the thiourea, and then reduce it to the aminal. I think you can use Ni hydrides for this. I know it works for cyclic thioureas, not sure about linear ones. Maybe worth looking into.

[Shadow]

Thiourea is nucleophilic on S. How would the synthesis work then?

[Dan]

Thiourea is nucleophilic on S. How would the synthesis work then?

Thioacylation of an amine with a thiocarbamoyl chloride, e.g. http://www.sigmaaldrich.com/catalog/product/aldrich/135895 is what I had in mind

[Shadow]

This would be the final version if the reduction works: (NiH2 instead of H2)

[Dan]

This would be the final version if the reduction works: (NiH2 instead of H2)

Yes, that's what I had in mind. I think you can use NiCl₂/NaBH₄ or Ni/H₂ for the reduction.