[PT]

I have vinyl cyclopropane diester compound. I need to convert one ester group to amide. I am thinking to do first making mono acid than acid chloride and finally amide from acid chloride. Because I did not want to affect my another ester group and vinyl group so which conditions are suitable for these reaction. Pls anybody suggest me.

[sjb]

I have vinyl cyclopropane diester compound. I need to convert one ester group to amide. I am thinking to do first making mono acid than acid chloride and finally amide from acid chloride. Because I did not want to affect my another ester group and vinyl group so which conditions are suitable for these reaction. Pls anybody suggest me.

Do you mean a malonate derivative, or are the esters on different carbons? You may be able to use some form of esterase to give some sort of chemo/stereoselectivity?

[Dan]

I am thinking to do first making mono acid than acid chloride and finally amide from acid chloride.

There is quite a lot of literature precedent for the ester hydrolysis - the ester trans to the vinyl group is selectively saponified in high yield with NaOH (Example [see supplimentary info]).

To play on the safe side, you could then do a DCC etc.-mediated amide coupling or activate the acid as a mixed anhydride with isobutyl chloroformate (the conditions for these reactions are milder than those used to make acid chlorides).

You could attempt selective amidation of the less hindered ester in one step by heating the diester with the amine directly - hydroxide attacks the ester trans to the vinyl group with high selectivity, so it is probably a reasonable assumption that an amine nucleophile might behave similarly. I would test this direct approach first because it is a much shorter route (but the feasibility depends on the bulk of the ester and the amine, which you have not mentioned).

[PT]

To Dan - Thank you so much for your suggestion. I will try both approach. I just want little clarification in direct heating for diester and amine. Should I require some catalyst/acid or base to activate reaction or simple heating is enough. I also don't understand that you also said that reaction feasibility depends on the bulk of the ester and the amine. Do you means amount do ester and amine or anything else.

To Sjb - Diester is attached to cyclopropane carbon which adjacent to carbon attached to vinyl group

[Dan]

Should I require some catalyst/acid or base to activate reaction or simple heating is enough. I also don't understand that you also said that reaction feasibility depends on the bulk of the ester and the amine. Do you means amount do ester and amine or anything else.

A catalyst is probably not required because the amine is basic, but a mild base (tertiary amine or carbonate salt) would not hurt.

By "bulk" I mean "steric hinderance"

[PT]

to Dan - Thanks for nice suggestion. I already got clean NMR of mono acid dvt. I will start two reaction one with acid and amine in presence of DCC. Second is ester with amine directly. Steric hinderance is possible due to bulky amine group. But I will try and see how it go.

[orgopete]

As I recall, the cyclopropane amino acid is synthesized from the diester with ammonia and Hofmann rearrangement. Malonates are more susceptible to nucleophilic attack so ammonia can react directly.