[jeanno]

Dear All,

I am facing a major problem for a simple amide coupling.

One side: The "amine" (1).
I have a R-NH₃⁺Cl^- that is only soluble in water.

The other side: The "acid" (2).
I have a methyl ester. I deprotect using LiOH in water:THF (1:1). The anionic form is soluble in water, MeOH, etc. As soon as I acidify the carboxylate it precipitates and the acid not soluble at all in any solvent (even not suspension in DMSO, DMF, mixture, etc...)

How would you perfom the amide coupling ?
Can we perform amide using the carboxylate form instead of the acid form ?
How "basifying" the protonated amine (1) ?

Thank you for your help

Jeanno

[discodermolide]

Dear All,

I am facing a major problem for a simple amide coupling.

One side: The "amine" (1).
I have a R-NH₃⁺Cl^- that is only soluble in water.

The other side: The "acid" (2).
I have a methyl ester. I deprotect using LiOH in water:THF (1:1). The anionic form is soluble in water, MeOH, etc. As soon as I acidify the carboxylate it precipitates and the acid not soluble at all in any solvent (even not suspension in DMSO, DMF, mixture, etc...)

How would you perfom the amide coupling ?
Can we perform amide using the carboxylate form instead of the acid form ?
How "basifying" the protonated amine (1) ?

Thank you for your help

Jeanno

Why not use the methyl ester directly?. Get a a solution of the free amine in an organic solvent, make it as concentrated as you can. Add it to the methyl ester, add a catalytic amount of NaCN and heat to 80-100°C in a sealed tube. The amino group is usually nucleophillic enough to do this reaction.

[AC Prabakar]

For direct amidation of ester lot of procedures availbale in literature!
U can get it from google also.
Try once!
Best of luck!

[jeanno]

Thank you for your mail and your help.

Ciao,

Jeanno