No worries, Assyl talks nonsense too from time to time.

The Schlenk line might be unnecessary, but who knows. These research labs seem to run everything under nitrogen by default, since it never hurts anyway, and ensures things stay dry. The Williamson ether synthesis can be done also with DMSO/NaOH, maybe that would be applicable here. The idea is to generate dimsyl sodium, which should be a strong enough base to deprotonate the 14-OH on naltrexone, etc.

Too bad there seems to be no reports on the activity of 14-O-cinnamyloxycodone/naltrexone/etc. Assyl has been interested in this one for a while, as it'd be able to swing free, unlike the cinnamoyl esters (conjugation from the opioid scaffold to the phenyl terminating the cinnamoyl means a planar and inflexible structure).

Either way, what you suggest here does sound like a solid plan - you make a good point, it's true that you might as well break open that CPM while you're reducing the cinnamoyl anyway. Cinnamoyl should be a better acylating agent than its reduced sibling, as sp2 hybridized carbons are somewhat EWGs and the key step of acylation is nucleophilic attack by the alcohol on the carbonyl carbon. The difference probably won't be terribly significant, but it can't hurt (unless there's something crazy Assyl isn't anticipating, which does happen too often in chemistry).

Honestly, you might want to methylate that 3-MeO before giving this a shot, as you may end up with something so ungodly potent (given the modification of CPM) that it could be obscenely hazardous to work with. Reeling that back a bit, at least for initial tests, is probably not such a bad idea. A dead bee is a shitty drug warrior bee - the dead can't type. It's probably going to be more lipophilic given the modification being considered, so transdermal absorption is a concern for sure.

Regarding crummy yields with cinnamylation via the I2 route - Assyl isn't really concerned about this. Thing is, the clandestine chemist confronts a scenario drastically different from the pharmaceutical chemist. The economics of the situation are entirely different. What had Assyl initially interested in this chemistry was actually modifications of oxycodone, the naltrexone came later (after discovering that paper attached on page 1 about phenylpropoxy ethers of naltrexone being highly active agonists). The idea was that the only type of precursor that can never be controlled or rendered unattainable is a "drug of abuse," as these are subject to black market forces that ensure their availability. Now, if 14-O-cinnamyloxymorphone is 8500-24,000x morphine (according to the Schmidhammer papers) then a mere 1% yield, two steps from oxycodone, means the potency of the material just jumped around 50-250x (depending how you compare the activity of morphine and oxycodone). Not bad at all. What would be considered a complete failure in a pharmaceutical lab could be a devastating success in the clandestine one.

It seems that the I2 procedure is generally viable. There's several reports in the literature of analogous chemistry, one of which is attached - note that p-chlorobenzyl alcohol affords slightly higher yields (88%) than benzyl alcohol (81%), suggestive of a cationic mechanism. It's essentially an unusual Friedel-Crafts alkylation. Another report is a paper from the Journal of the Indian Chemical Society which, unfortunately, is not online, as they only entered the 21st century in 2008, and which is, unfortunately, not attached, as Assyl has yet to enter the 21st century. But either way, they prepared benzyl and cinnamyl methyl ethers using cinnamyl and benzyl alcohol and I2 with trimethyl orthoformate, and the yields were high, 80-90% across the board. The reaction only worked with cinnamyl and benzyl alcohols, consistent with the mechanism proposed previously. Can't remember if they tried allyl alcohol.

We now describe a potent opiate analgesic lacking the traditional side effects associated with classical opiates, including respiratory depression, significant constipation, physical dependence, and, perhaps most important, reinforcing behavior, demonstrating that it is possible to dissociate side effects from analgesia.

Sounds like it's no fun.

Thanks for that. Been looking for that paper for a while now.

What Toady would love to know is if they are partial or full agonists at this hMOR  splice variant.

As long as they are full agonists, then some of these might just be ideal for him. Oxy isn't all that great. Addictive, constipation-forming, and tolerance is a bitch (at least, going from being able to shoot one 40mg to needing at least 5x80s is)

Seeking something that doesn't come with a ball and chain round my ankle.

Sure, euphoric, dependence-free opioids you can still take a shit on would be great....this one does look good though. And its not as if I have to worry about euphorigenic potential. I' on a free, longterm OC 80 script.

Problem is, I HAVE to take the stuff, if I don't, the withdrawal is incapacitating. I can barely even type right now, thanks to an unrelated episode of vomiting and myoclonic seizures. Something environmental has been causing repeated vomiting, I suspect either Zn, Pb, Cu, Cd, or possibly Ag fumes from metalworking, Toadface does that on the side to make his disabity pittance something that its possible to live on, rather than barely eke out an existence, dependent on family being willing to keep a roof over his head and on occasion, food at his table.

he has recently had so many fucking bouts of throwing his insides up, that he has had to get replacement scripts so many times, his doc won't cover that any more, he is decent guy, but there are limits even to his charity.

He just doesn't want to have to deal with timing his oxy doses so there is no WD period, or run out a few days early, due to having to take a couple extra if he HAS to walk any significant distance.
(ATM. he is on OC80s, oral indomethacin, topical naproxen and steroid shots intraarticularly., and a shitload of strong muscle relaxant, high-dose tizanidine, which as he is already taking clonidine and  chlormethiazole, is one hell of a myorelaxant, enough to knock him clean out at times, but walking further than the local shops, still, is absolute agony.


Whereas before his leg got so bad, he'd spend all day, many days, hiking in the woods looking for wild mushrooms

Its just that pain relief has been elusive. And of course, homeostasis is a bitch.

FFS, FENTANYL put me in withdrawal, having been tested on it and not given enough.

Of course I enjoy a nice big fat 0.5g shot of IV oxy, but euphoria? I would trade it all, permanently, for the ability to walk where and when I want, for how long I want, if thats the choice I had to make.

Right now, after shooting 2 OC 80s, ever step I take, it feels like having white hot nails driven into the back of my knee.

Fell on glass playing in an abandoned factory as a kid, then as I was recovering, about 20 fucking pikey tossers stamped on me repeatedly.

I have BEEN on fent patches. They sucked ass. Took hours to kick in when used as intended, transdermally, and my doc wouldn't even think of giving me any more than the lowest possible dose, 12.5ug/hour.

I got given 4 patches, 3 to last until the next rx due, and one spare lest they fall off, as transdermal patches like to do. With my oxy tolerance, wearing one patch, or two of them didn't even do more than take the edge off the withdrawal from no oxy. Luckily I had one OC 80 left, so I shot the patches, used the oxy and went in the day after begging to be put back on the oxycontin. The patches were so little, that they didn't so much as scratch the surface of my tolerance or pain levels. It was alright at 0.5-1mg IV, but meh, pure selective Mu1Or agonists aren't actually all that good.