Author Topic: deschloro loperamide (Read 1365 times)

Dope Amine · « **Reply #40 on:** January 22, 2012, 12:56:19 AM »

Also, with regard to the neurotoxity issue, it was concluded that only N-methyl analogs had this potential to be converted to MPTP type neurotoxins. Under the Wiki entry for PEPAP they cite a study which found:

Quote

It appears that the N-methyl group of MPTP is required for neurotoxic activity. In animal experiments, only MPTP analogues that preserved the N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine structure were active as dopaminergic neurotoxins. Most structural changes, including replacing the N-methyl group with other substituents, abolished neurotoxicity.[3]

So.... it may be a bit of extra work but I'd really like to know the pharmacological outcome of switching the dimethyl amide to the ethyl ester. The only risk I believe there might be in 1. hydrodechlorination, 2. alcoholysis, and 3. making the propionyl ester is that besides making an über strong analog, it could have too long of a duration (thus causing rapid tachyphylaxis like some of the long-acting fentanyl analogs). OR it could be that getting rid of that damn dimethyl amide and replacing it with something more useful is just what is needed to make it a damn euphoric compound! There's only one way to find out.

Alcoholysis rxn conditions would be (I believe) refluxing the deschloro-Lop in dry EtOH with a bit of H₂SO₄.

jon · « **Reply #41 on:** January 22, 2012, 03:26:47 AM »

yeah but did you look at the conditions?
it takes a lot of energy, i tried that with ethyl acetate and sulfuric acid but i could'nt tell you if it worked i don't think it's even nessecary

Dope Amine · « **Reply #42 on:** January 22, 2012, 08:25:22 AM »

My understanding is that refluxing dry ethanol with a strong acid is a superior means of obtaining the ethyl ester. I do not think you made the ethyl ester using ethyl acetate.

Sedit · « **Reply #43 on:** January 22, 2012, 02:36:59 PM »

Quote from: EverlastingReign on January 21, 2012, 08:47:35 AM

Quote from: Sedit on January 21, 2012, 05:17:27 AM
Not exactly fun but no doubt active. It did however feel toxic but I want to stress, we DO NOT... want to kill the PGP ability of this as I believe they are the only thing protecting from Loperamides toxic metabolite. This can still be ushered out of the brain though this wonderful transporter instead of staying in the cell destroying it. This is good new and bad news.... It means the toxic effects will not show up right away and will only appear after prolong use as opposed to the frozen addicts case of Demerol analog from hell which had nothing to transport it out and it got stuck showing Parkinson withing days.

I believe the danger in this case is overstated.

I agree that the dangers maybe over stated but they one study they performed using baby pigs who have yet t develop a BBB instantly started to show signs of toxicity due to the formation of what they call LPP+ which is the analog of the typical neurotoxin found in these other drugs we know and love.

Dope Amine · « **Reply #44 on:** January 22, 2012, 07:09:18 PM »

Well shit, that sounds like a pretty good point. Could you please point me in the direction of said article?

Dope Amine · « **Reply #45 on:** February 03, 2012, 06:11:23 PM »

Jon, I'm hoping you can help me out here. So I've extracted and gotten more than my theoretical yield (roughly .5 g instead of .384 g) because I have green gunk instead of pure white powder. I've tried toluene, acetone, denatured ethanol, IPA and combinations of those. Always there is green crap, both sitting at the bottom and in solution. Any recommendations?

Supposedly the hydrochloride is very slightly soluble in cold water so my next plan of attack was to try to dissolve in hot water and then cooling it down to near 0° C and hope that the green crap stays in solution. Maybe add some brine prior to cooling.

jon · « **Reply #46 on:** February 03, 2012, 08:39:18 PM »

use isopropanol as a recrystallization solvent.
use boiling ipa.
if you want to force recrystallization drive it out of solution with acetone.
also when you extract from pills the loperamide is bound to hypomellose as a complex so you won't get it all just using methanol.
first make a slurry with boiling water, then extract the pill mass with methanol.
the boiling water will break the complex.

Dope Amine · « **Reply #47 on:** February 07, 2012, 08:28:55 PM »

Okay, so I finally figured out a very easy method to get super-pure lope quickly from those pills.

Loperamide HCl is freely soluble in alcohols, minimally soluble in cold water, and I would think it should be practically insoluble in cold acetone just like fentanyl HCl but I have not yet observed this. I did observe an IPA solution of Lope get cloudy when I squirted in some water but it wasn't sizable enough to be worth bothering to filter.

The green gunk is highly soluble in acetone, somewhat soluble in alcohols, and very slightly soluble in hot water. I discovered the water bit when I heated an alcohol/water solution up to about 80 deg. C and the majority of the green gunk coagulated and stuck to the side of the beaker. I filtered this and got a light green powder after it was evaporated to a minimal volume. But what was really exciting was when I took that dirty beaker with the green gunk on the sides, added MeOH and then acetone to get it all into solution and then I added some activated carbon and let it sit. In a half hour that green solution turned completely clear! So here's the short and sweet method:

Grind up the Lope pills in a small amount of distilled water and heat to ~80 degrees Celsius with manual stirring . Add MeOH or denatured EtOH to double the volume, stir, let settle and then syringe/pipette off the clear top portion. Repeat the alcohol extraction twice more. Add activated carbon (also known in certain locales as "activated charcoal") to the pooled extracts and gently stir until solution goes from green to completely clear. Filter and place the filtrate on low heat to evaporate down to a minimal volume at which time it will crystallize out and you can break up the chunks to let it dry out further. That's it! No need to filter the Lope from a dirty mother liquor and lose product in washing the crystals. The activated carbon really does an amazing job of absorbing all of that green crap.

jon · « **Reply #48 on:** February 07, 2012, 09:55:00 PM »

very good

opanda · « **Reply #49 on:** February 12, 2012, 07:55:12 AM »

"Grind up the Lope pills in a small amount of distilled water and heat to ~80 degrees Celsius with manual stirring . Add MeOH or denatured EtOH to double the volume, stir, let settle and then syringe/pipette off the clear top portion. Repeat the alcohol extraction twice more."

-could MeOH be replaced with 99% isopropyl alcohol?
-should the solution be kept boiling while adding the alcohols through all 3 extractions?

Dope Amine · « **Reply #50 on:** February 12, 2012, 08:07:34 AM »

First off, I would like to say that Lope HCl is definitely soluble in acetone. This has been observed.

So, a test CTH hydrodechlorination reaction was run with 0.31 g Lope HCl. This is ONLY 0.000604 moles or 0.604 mmol so it was not possible to accurately measure the appropriate amounts of Pd/C 10% (1% moles Pd) or 3x molar excesses of KOH and formic acid using a scale that only read to .01 g. So they were all added at a greater excess. The methanolic solution was slightly acidic (pH~5) and was pre-stirred prior to adding the white needles of Lope HCl which had been obtained by crystallization from a minimal aqueous solution. Anywayz, here's the real concern. ALWAYS when doing a CTH reductive amination there was vigorous bubbling of carbon dioxide from the reduction taking the two hydrogens from HCOOH and releasing said CO2. This time when the Lope HCl was added there were no bubbles noted. The only explanation I can think of is that the molar concentration is so low that the CO2 production is so minuscule that is is just dissolving into the methanol and not generating bubbles. But I am very concerned that I am not witnessing a reaction taking place. CTH reductive amination is cakewalk, very hard to fuck up, pre-stir or not. One time I added the Pd/C last and it almost volcanoed on me! Anywayz, enlightening thoughts would be greatly appreciated. K+ and HCl are the other side products, but there will not bee enough moles of HCl (.000604) in a roughly 180 mL solution to make a difference such that I could check the reaction via the pH dropping.

jon · « **Reply #51 on:** February 12, 2012, 11:44:32 PM »

the examples i see use 5% mole ratio of pd/c/substrate.
your loading must be low and that's why you're not seeing CO2 gas.
also you say the methanol was acidified with hcl it is possible that you displaced formic acid from the salt which is a poor hydrogen donor.
but i suspecct it's your loading.
the above example uses 5%

Dope Amine · « **Reply #52 on:** February 13, 2012, 02:48:45 AM »

It's acidic cuz there was more moles of formic than KOH. The only HCl is on the Lope. I later added 20 mL of dH₂O cuz I remembered that usually it's a 10% aqueous alcoholic solution. For some reason the water is supposed to help. I will add a bit more 10%Pd/C and then I will definitely be over the 5%, maybe even 10%. I prolly already have at least 3% cuz I added more than what was called for for 1%. Anyway, I'll let that stir with more Pd/C for 3 more hours and then it's work-up time: Filter through celite, reduce volume by recovery of methanol, add brine and extract 3x with DCM. The Lope HCl should go right into that. Evaporate down and see what's there.

There is a really great article that I used to have but no longer have access to. If somebody could get it it'd be greatly appreciated. It's a Chemical Reviews article on CTH, including dehalogenation among all the other uses: Chem. Rev., 1974, 74 (5), pp 567–580

Potassium formate is THE most effective reducing agent of all the formic salts. I dunno why ammonium formate has always been so much more popular.

jon · « **Reply #53 on:** February 13, 2012, 03:10:33 AM »

sounds like a reasonable workup strategy.
water participates in the transfer reduction in the case of alkali formates in the case of ammonium formate it decomposes to CO2 and H2 without any water present.
another thing you say the overall volume of your solution is ~ 200ml?
the reason your reaction may be going at a crawl would be due to chemical kinetics.
this reaction exhibits first order kinetics relative to the concentration of the formate ion.
to remedy this increase the concentration of potassium formate.
also i noticed you did'nt employ an inert atmosphere.
this may be fine if you are doing a large scale reaction because the CO2 will blanket the RXN but with a smaller scale like this it could hinder it.

Dope Amine · « **Reply #54 on:** February 17, 2012, 03:35:44 AM »

Here's that great review article.

jon · « **Reply #55 on:** February 17, 2012, 03:48:14 AM »

did your reduction work out?
silly me i had that article i went scouting for it and i had it all along.

Dope Amine · « **Reply #56 on:** February 19, 2012, 08:34:17 PM »

70 mg insulfated and all I can really report is that the next day I didn't take my regular like clockwork morning shit after my regular morning cup o' coffee.

I believe the CTH reaction needs refluxing 10% aqueous methanol to go. Hopefully that much water would still keep the temp. well below 80 deg. where you say it is possible to CTH off that hydroxyl. Either the reaction didn't go at r.t. or else deschloro-lope is a dud without that propionoxy group.

jon · « **Reply #57 on:** February 19, 2012, 11:07:40 PM »

well we know it has some activity the papers say it is about 1/2 as active as morphine so i would'nt expect much.
it does have a long half-life (about 14 hours) so not taking your morning medicine would make sense.

Dope Amine · « **Reply #58 on:** February 20, 2012, 03:15:09 AM »

Hmmm interesting. I did mean the statement above to be taken literally (my bowel movements are very regular and in the morning), although I do consider my morning dosage to be like my morning cup 'o coffee. But interestingly, I didn't feel the need for that as much as I normally do. So who knows, chalk it up to somebody that already has a high tolerance: 40 mg methadone is my stabilizer, but I could easily do 60 mg or more.

It's the evening and I still haven't shit and don't feel any need to so I'm def. constipated!

jon · « **Reply #59 on:** February 20, 2012, 06:16:03 AM »

well with the propionoxy ester 10 milligrams was enough to break through 60 milligrams of methadone so it binds strongly to opiate receptors.
and it packs a pretty good punch for 10 milligrams to do that.
i would like to see what happens when des-chloro loperamide is esterified with p-anhydride.

Author Topic: deschloro loperamide (Read 1365 times)

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