Help with Tropacocaine

[azabicyclo]

Tropacocaine (8-methyl-8-azabicyclo[3.2.1]oct-3-yl) benzoate

Can anyone please offer any knowledge/ help in transforming the above material into :
methyl (2R,3S)-3-benzoyloxy-8-methyl-8-azabicyclo[3.2.1]octane-2-carbo
xylate

Is this possible? does any one know? What is the method , if it is at all possible ??

All help greatly appreciated..

 

[vecktor]

Tropacocaine8-methyl-8-azabicyclo[3.2.1]oct-3-yl) benzoate
AKAs,s,s)-2-azabicyclo[3,3,0]-octane-3-carboxylic acid benzylester hydrochloride

Can anyone please offer any knowledge/ help in transforming the above material into :
methyl (2R,3S)-3-benzoyloxy-8-methyl-8-azabicyclo[3.2.1]octane-2-carbo
xylate

Is this possible? does any one know? What is the method , if it is at all possible ??

All help greatly appreciated..

it is not possible to convert tropacocaine into cocaine by any practical method. it is very difficult to insert the methoxycarbonyl (methyl carboxylic ester) or a carboxlic group at the right position 2 and the right way up (beta)

p-fluoro tropacocaine (4-fluorobenzoic acid ester) is more potent and cocaine like,possibly 1/3 the activity of cocaine, it is though a much more potent ion channel blocker and so most likely is just as toxic as cocaine.
search for the post by FastandBulbous and there was some discussion about it.
I am not sure whether tropacocaine has been widely used outside of medicine, it has appeared as a cut in cocaine because it passes the chlorox test.

 

[azabicyclo]

Hey, somebody who knows about it.
You say any practical method.
What about impractical
Is it possible?
What is Tropacocaine as it seems to create a similar feeling to cocaine only it is more , well plant like in odour.

I have the hcl.

You say difficult to insert the methoxycarbonyl.
How difficult?
What would the method and materials be?
Please expand on your very helpful answer:

 

[Tehuti]

active?

Isant Tropacocaine active?

 

[haribo1]

The 4-fluoro analog is the one to go for. It's supposed to be 40% the activity of cocaine with a similar buzz but slightly longer acting. I would also consider making the C-C bonded version (instead of the benyl ester). That should be stronger again & MUCH longer acting. It should also be orally active so your injestion methods open up somewhat.

 

[vecktor]

Hey, somebody who knows about it.
You say any practical method.
What about impractical
Is it possible?
What is Tropacocaine as it seems to create a similar feeling to cocaine only it is more , well plant like in odour.

I have the hcl.

You say difficult to insert the methoxycarbonyl.
How difficult?
What would the method and materials be?
Please expand on your very helpful answer)

there is a no synthesis policy on BL, but a vague discussion is OK,

basically the problem is that if you can get the materials and have the skill to turn tropacocaine into cocaine then you would also be able to get hold of other more suitable precursors, like tropinone. And also you would soon realise that cocaine is not too potent and that there are other things like the WIN tropane series which are much more potent and more attractive.
Anyway my opinion has always been if you want coke buy coke, and if you want pure coke then purify street coke, it is always going to be cheaper and easier.
the two papers below have all the information you need..
Satendra Singh
Chem review 2000 100 925-1024
http://www.erowid.org/archive/rhodium/pdf/cocaineanalogs.pdf

and for the insertion of 2-methoxycarbonyl

J. Org Chem 1995 60 5825-5830
http://www.erowid.org/archive/rhodium/pdf/2-carbomethoxytropinone.stereoselective.pdf

the p-fluoro compound is simply made by hydrolysing tropacocaine with base and reacting with p-fluorobenzoic acid.

p-fluoro probably helps by forcing the tropacocaine into a better configeration in the binding site on DAT in the abscence of anything sticking out of the 2 position, 3,4-dichloro substitution has also worked on some other poorish DAT ligands.