etorphine synthesis questions

[pickle11]

in future synthetic drugs of abuse it says that etorphine is made with thebaine (which can be made from codiene

https://www.thevespiary.org/rhodium/Rhodium/chemistry/oxycodone2.html

) methyl vinyl ketone (doesn't sound too hard) and "the proper grignard reagent."  What is the grignard regeant in question?  What if you used other p2p's instead of methyl vinyl?  What if you used other organomagnesiumhalides?  Is there any chance of mptp contamination?  There are conflicting reports about the potency.  Some say 1000x more potent than morphine, some say 25,000x.  I think a liquid solution would be the best method of administration.

[Rhodium]

If you can't tell your chemicals apart, you should not be messing with ethorphine.

MPTP is only formed in the synthesis of MPPP (the reverse ester of pethidine) if you don't do it right.

[nightshade]

I looked on TSE here,and looked on the TSE there and there seems to no info concerning etorphine anywhere. I read somewhere it is a two step process,so what is the process.
This is same stuff the russians used on the opera house yes.
What is the ETORPHINE SYNTHESIS please.

[Rhodium]

The opera opiate was a fentanyl derivative. For etorphine see below:

Post 207133 (missing)

(slappy: "Re: Etorphine?", General Discourse)

http://www.greensponsors.com/NovartisWeb/M99Science.html

[nightshade]

Yes I have read that etorphine was discovered in 1963 , patented in 1967 by a man Bentley. No where have I found anything posted about how to make it, future drugs of abuse says it is two step process. Does anyone know what the two step etorphine synthesis is?

[nightshade]

Bentley posted his discovery in J.Amer.Chem.Soc 1967,89,3281-3292
Something about the Bentley compounds made from thebaine some being the most powerful known to man.
Could someone post the synthesis for etorphine.

[Rhodium]

Novel analgesics and molecular rearrangements in the morphine-thebaine group. I.. Ketones derived from 6,14-endo-ethenotetrahydrothebaine
Kenneth W. Bentley, Denis G. Hardy

J. Am. Chem. Soc. 89(13); 3267-3273 (1967)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/bentley-1.pdf)

Novel analgesics and molecular rearrangements in the morphine-thebaine group. II. Alcohols derived from 6,14-endo-etheno- and 6,14-endo-ethanotetrahydrothebaine
Kenneth W. Bentley, Denis G. Hardy, B. Meek

J. Am. Chem. Soc. 89(13); 3273-3280 (1967)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/bentley-2.pdf)

Novel analgesics and molecular rearrangements in the morphine-thebaine group. III. Alcohols of the 6,14-endo-ethenotetrahydrooripavine series and derived analogs of N-allylnormorphine and -norcodeine
Kenneth W. Bentley, Denis G. Hardy;

J. Am. Chem. Soc.; 1967; 89(13); 3281-3292.

(https://www.thevespiary.org/rhodium/Rhodium/pdf/bentley-3.pdf)

[nightshade]

Now the question I have concerning this article pages 3281-3292 doesn't say anything about refluxing thebaine with methyl vinyl ketone (1000grams in 3 liter) followed by grignard reaction. The paper before this one does and it is is by the man. So etorphine is made by refluxing thebaine in mvk followed by a grignard reaction? Then used as is or is made into a salt?

[nightshade]

Could some one also post the other two papers that are the three part series by the same author-same journal,please?
And could someone break down the synthesis please.

[Rhodium]

I added the two other papers to

Post 451151

(Rhodium: "Etorphine synthesis", Methods Discourse)

And could someone break down the synthesis please.

Don't you think that is a bit too much to ask, when you have gotten the whole article series collected for you?

[bobot]

Has anyone had a chance to review these synthesises,and post a step by step synthesis of this compound.

[slappy]

Are you kidding? That's like giving a loaded handgun to a hyper-active three year old. If you can't discern the synthesis from reading the papers, chances are that your chemical hygiene techniques are not sufficently advanced to prevent killing yourself anyway.

This is besides the fact that Etorphine has never, and probably should never be used in humans. Keep in mind that the dose to put down a rhino is 5mg, and even that can send the animal into respitory failure! Go to the link that Rhodium posted (novartis) and read the handling procedures.

[Rhodium]

Synthesis and Biological Evaluation of 14-Alkoxymorphinans. 20. 14-Phenylpropoxymetopon: An Extremely Powerful Analgesic
Johannes Schütz, Mariana Spetea, Martin Koch, Mario D. Aceto, Louis S. Harris, Andrew Coop, and Helmut Schmidhammer

J. Med. Chem. 46(19), 4182-4187 (2003)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/14-phenylpropoxymetopon.pdf)
DOI:

10.1021/jm030878b

Abstract

The synthesis and the biological and pharmacological evaluation of several 14-phenylpropoxy analogues of 14-methoxymetopon are described. Most of the new compounds were nonselective and exhibited binding affinities in the subnanomolar or low nanomolar range at opioid receptors (mu, kappa, sigma), with 14-phenylpropoxymetopon (PPOM; 7) displaying the highest affinity for all three opioid receptor types. The most striking finding of this study is that the derivatives from the novel series of N-methyl-14-phenylpropoxymorphinans acted as extremely powerful antinociceptives with potencies higher than that of 14-methoxymetopon (1) and even etorphine. 14-Phenylpropoxymetopon (PPOM; 7) showed considerably increased potency in the in vivo assays in mice (25-fold in the tail-flick assay, 10-fold in the hot-plate assay, and 2.5-fold in the paraphenylquinone writhing test) when compared to etorphine, while it was equipotent to dihydroetorphine in the hot-plate assay and the paraphenylquinone writhing test and ca. twice as potent in the tail-flick assay than this reference compound. The 3-O-alkyl ethers of PPOM, compounds 6 and 8, showed less potency in in vivo assays, but partly surpassed the potency of the 3-OH analogue 14-methoxymetopon (1).

[nightshade]

In the book "OXY" by Otto Snow there is a break down on the etorphine synthesis the thing that is missing is the method of making the HCL salt of etorphine.