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Naltrexone -> Oxymorphone?

- Thu, 17 Mar 2016 18:16:02 EST GksK9UMc No.77752
File: 1458252962747.png -(55460B / 54.16KB, 992x379) Thumbnail displayed, click image for full size. Naltrexone -> Oxymorphone?
Dear /chem/,

wikipedia cites that "Naltrexone can be described as a substituted oxymorphone – here the tertiary amine methyl-substituent is replaced with methylcyclopropane. Naltrexone is the N-cyclopropylmethyl derivative of oxymorphone."

Is it possible to revert naltrexone back to oxymorphone? If so, how?

My very limited understanding of organic chemistry leads me to believe that naltrexone could, in proper solution and (probably) with the addition of heat, be broken into oxymorphone and cyclopropylmethylbromide. (pic related)

Any input regarding said (hypothetical) reaction will be greatly appreciated!
Bombastus !RZEwn1AX62!!xXxJO70U - Sat, 19 Mar 2016 09:50:52 EST 4ppVjZXo No.77753 Reply
Don't let the wikipedia page fool you. Amine opioid chemistry is one of the most annoying parts due to the de-alkylation possibly breaking the bridge right off.
N, dealkalation. Would not be selective and you'd get an incredibly low yield for any sort of literature backed N, dealkylation despite the non-cyclic alkane-functional group being more sterically favored.

Demethylation of natural opiates is already messy enough despite it being much more sterically favored. If you're trying to de-alkanate a large molecule cyclopropylmethyl-, you'll have all sorts of messes going around.

This "drug metabolism" course I found on Google gives a pretty good idea of the selectivity and complexity in real world amine chemistry:
Note that:
>small alkyl groups e.g. methyl, removed rapidly.
This is why you can achieve nor-x-orphone really easy. x being m, oxym, hydrom, etc.
>α-carbon involved has to be attached to a hydrogen atom.
Which means that the nitrogen bridge would have as much selectivity as the other carbon of interest. This would leave your yield to be a theoretical max. of something like 30%. This isn't even counting the backside attack on the exposed morphinan group!
Ru-lover - Sat, 26 Mar 2016 19:06:51 EST 1yz9Gpwk No.77772 Reply

Hi, you cannot remove the cyclopropylmethyl group of the amine, by the way naloxone is another antagonist that contains an allyl group. This latter can be easily removed with the help of precious metal (Pd for example) catalyst and replaced with methyl to make oxymorphone.

I suggest to treat nalloxone with MeI in alcohol or DMF and collect the precipitate : this is nalloxone methiodide.

There are a lot of example of de-quaternisation of salt with thiolate salt in aprotic polar solvent.

The nalloxone methiodide can be heated in DMF or DMSO with dodecanethiol qunched with 1 eq of base such as tBuOK. The DodSK will cleave the allyl group in preference for the methyl here to give oxymorphone !!
Bombastus !RZEwn1AX62!!xXxJO70U - Sun, 27 Mar 2016 13:18:03 EST 4ppVjZXo No.77773 Reply
Didn't you start your comment by saying that "you cannot remove the cyclopropylmethyl group of the amine" and then go on and say how to remove that group? Correct me if I misunderstand, please.

If I understand correctly, I don't see why it would. The less sterically-hindered ethylene-amino bridge be cleaved vs the cyclo-propyl (more hindered) group?

However, I guess using a sterically selective agent like dodecanethiol would help. You're right that the alkyl group would fall apart but which one? Isee the ethylene bridge snapping apart before the methylcyclopropyl group is even touched with an equilibrium of 1:1000 or greater
Vehk !7HYGxe5v5c - Mon, 28 Mar 2016 10:59:30 EST mqpMZrCV No.77774 Reply
1459177170548.jpg -(38976B / 38.06KB, 463x411) Thumbnail displayed, click image for full size.

OP was talking about naltrexone, which contains the methylcyclopropane substituent, the guy above you is talking about naloxone, which shares the same structure as naltrexone except with an allyl group instead of a methylcyclopropane group forming the substituent.

See picture for reference.
Fanny Munkinspear - Wed, 30 Mar 2016 11:18:57 EST 8U0GcjC9 No.77775 Reply
>in real world amine chemistry:
I read this is "in real anime world chemistry"
Ru-lover - Wed, 30 Mar 2016 19:13:14 EST 1yz9Gpwk No.77777 Reply
Thanks for clearing this up. Its exactly what I am talking about. Allyl group is 1000x easier to remove than cyclopropylmethyl. You can also use wilkinson catalyst, there are some papers about that.
Cornelius Bushwen - Sun, 10 Apr 2016 22:52:26 EST ljoFE2/4 No.77821 Reply
Quints don't happen here but once in a great while.
Marty Poppenheimer - Sun, 01 Jul 2018 00:46:46 EST D3AAbMyr No.79156 Reply
1530420406530.jpg -(227009B / 221.69KB, 1680x1050) Thumbnail displayed, click image for full size.
Would someone mind explaining this process in a way that a significantly more retarded person could understand?

>Treaet Naloxone with Mel in Alcohol, or DMF
What is Mel? What is DMF?

Once you achieve this, you collect what remains from this process, which is Naloxone Methiodide.

>Heat your Naloxone Methiodide in DMF or DMSO
What is DMSO?

>With dodecanethiol qunched with 1 eq base, such as tBuOK
What is Qunched? What is tBuOK?

>t. retarded brainlet with Suboxone Tablets
Any help would be appreciated because I can't get shit out of these. I can follow basic instructions however.
Molly Nadgedale - Sun, 01 Jul 2018 20:46:17 EST OdR7meD+ No.79157 Reply
Google is your friend. Show the minimum effort at least.
Piemaster - Fri, 06 Jul 2018 05:57:39 EST pv6fN59z No.79162 Reply
Would it be possible to turn the cyclopropane into a terminal alkene using aluminum or something? I know cyclopropane's are very unstable.

And then would it possible to attach a carbon to the terminal alkene? You could attach a phenyl or something and make n-phenylpropyl.

Basically to sum up what I'm saying, instead of trying to remove the cyclopropylmethyl group outright, would it be possible to turn it into a 4 carbon chain, the last C=C being a double bond? And then using the reactivity of said double bond to attach something? You'd be able to make a pretty potent agonist that way.
Alice Honeyhall - Mon, 09 Jul 2018 03:51:31 EST mH/x48p3 No.79163 Reply
Cyclopropanes are very unstable but the one pictured with a stabilized alkane group is not. This group shown with an R-cyclopropane is relatively stable.
Carbon-carbon chemistry is very hard. Even harder to do selectively.

Short answer is most likely, no.
Edwin Clarryforth - Tue, 18 Sep 2018 23:44:00 EST y5OCfqyd No.79231 Reply

The cyclopropylmethyl can be turned into isobutyl via palladium under hydrogen. How hard would it be to remove it then?
Pressbastus - Sat, 20 Oct 2018 04:33:55 EST L5efXmCV No.79257 Reply
oh yeah how have we been going with this? OP did you make any significant literature readings or apply common reactions to make this even remotely practical?

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