Author Topic: Improved Cocaine synth  (Read 2810 times)

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tropine

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Improved Cocaine synth
« on: May 30, 2003, 10:26:00 PM »
After some review of the document on Rhodiums site of cocaine synthesis, one might note a few glaring errors, that must have been put in to sway the amature.  Assuming you can get to the methylecgonine step, we come to where the author suggests using 10 grams of RaNi for ~5 grams of material, which sounds like overkill.  He then suggests a Li hydride, but we all know that could destroy our lovely methyl ester family, so we come to our old selective friend NaBH4!  1 Mole Methylecgonine + 1 Mole NaBH4 in EtOH stirred at room temp for say 3 hours, then quenched with 10% H2SO4 would do the trick? Comments?

Megatherium

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A cocaine synthesis, huh?
« Reply #1 on: May 31, 2003, 02:53:00 AM »
For those who are serious about a from scratch stereospecific cocaine synthesis, read

Patent US6486323

:

Process for producing optically active tropinonemonocarboxylic acid derivative


Abstract

An optically active tropinonemonocarboxylic acid ester derivative useful as an intermediate for synthesis of optically active tropane derivatives was obtained by reacting succindialdehyde with an organic amine and acetonedicarboxylic acid ester to obtain a tropinonedicarboxylic acid ester derivative, and then subjecting this derivative to enzyme-catalyzed asymmetric dealkoxy-carbonylation. Since anhydroecgonine methyl ester derived from the optically active tropinone-monocarboxylic acid ester derivative by reduction and dehydration had the same direction of optical rotation as in the case of anhydroecgonine methyl ester obtained from natural cocaine, it was proved that the obtained optically active tropinonemonocarboxylic acid ester derivative had the same absolute configuration as that of natural cocaine. The yield of the optically active tropinonemonocarboxylic acid ester derivative from the asymmetric dealkoxycarbonylation was 30 to 50 mol %, and its optical purity was 70 to 97% ee. In addition, it was found that a crystalline optically active anhydroecgonine carboxylic acid ester derivative can be obtained by reducing and then dehydrating the optically active tropinonemonocarboxylic acid ester derivative and that its optical purity can easily be increased by recrystallization.

roger2003

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cocaine synthesis
« Reply #2 on: May 31, 2003, 10:14:00 AM »
Findlay has published a simple synthesis in

JOC 1957 p. 1389 pp

terbium

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Stereospecific!
« Reply #3 on: June 01, 2003, 06:50:00 AM »
Findlay has published a simple synthesis in

JOC 1957 p. 1389 pp

This includes a stereospecific synthesis of the (mono)carbomethoxytropinone? I don't think so! I am familiar with most of the literature on this up until the early 80's and don't remember a good stereospecific synthesis. In fact, if I had a little more time tonight, I could probably dig this Findlay paper out of my remaining archives.

I had considered the enzymatic decarboxylation of dicarbomethoxytropinone when I was working on cocaine synthesis but then the Columbians knocked the bottom out of cocaine prices and I abandoned the pursuit. It is heartening to see that someone has had success with the stereospecific enzymatic decarboxylation.


roger2003

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cocaine synthesis
« Reply #4 on: June 01, 2003, 11:14:00 AM »
Findlays synthesis of the (mono)carbomethoxytropinone is a one pot synthesis, that`s what i remember

Rhodium

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Findlay's 2-carbomethoxytropinone synthesis
« Reply #5 on: June 01, 2003, 05:57:00 PM »

Post 488336

(Rhodium: "Synthesis of Tropinone & 2-CMT", Methods Discourse)

terbium

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Findlays synthesis of the ...
« Reply #6 on: June 01, 2003, 06:31:00 PM »
Findlays synthesis of the (mono)carbomethoxytropinone is a one pot synthesis, that`s what i remember
Yes, and a very facile synthesis it is, but as you can see from the PDF that Rhodium has posted, it is a synthesis of racemic (mono)carbomethoxytropinone or the prochiral dicarbomethoxytropinone.

The subject of the first post in this thread is the production of optically active carbomethoxytropinone which, AFAIK, had not been described in the literature at least prior to the early 80's.


politoxicomania

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stereospecific
« Reply #7 on: September 11, 2003, 09:55:00 PM »
since 1900 up to nowadays nobody published a stereospecific reaction to cocaine which could be more useful as the robinson reaktion
terbium is right that findley doesnt give a stereospecific reaktion but he discribed the Tartaric way, which is stereospecific
the fact that robinsons preparation of 2-carbomethoxytropinone has high yields up to 90% makes it still the best and easiest way
the problem of the possible 8 isomeres of 2-carbomethoxytropinone is solved in protic solution
none of the stereospecific methods i found was as cheap as the robinsons method 
but enzymatic decarboxylation of the dicarbomethoxy-tropinone seems to be very interesting
are there any refs about this ? ::)