Author Topic: Pholcodine ----> Hydromorphone, 2-Step (Read 251 times)

Waggledance · « **on:** June 15, 2012, 11:44:08 AM »

#Not an original idea - Credit to Borohydride at Opi#

1) Hydrogenation of Pholcodine with RuCl3, Argon purge, H2O/EtOH : US Patent Application 12/886,621

2) Clevage of propylmorpholine with HBr, H3BO3, Argon purge : US Patent 4,667,037

Should give Hydromorphone.

Plan on running it soon, just thought I would look for some input. Only step I was worried about was clevage, books say 2 eq. HBr (47%), BF4, 115*C, 5-20 hours. Thinking this will be to harsh for hydromorphone so plan is ~ 4 eq. HBr (28%), H3BO3, Argon purge, gentle reflux below 80*C, 5 hours. (not sure on temp yet, probably a lot lower)

Balkan Bonehead · « **Reply #1 on:** June 16, 2012, 01:13:12 AM »

Problem: pholcodine is schedule I in the jewnited snakes

Waggledance · « **Reply #2 on:** June 16, 2012, 02:37:13 AM »

Ah yes, a problem for others indeed. Luckily for me 200mL at 15mg/5mL equiv to 11 of your jew dollars.

Alchemyst · « **Reply #3 on:** June 25, 2012, 11:34:04 PM »

Can this be done with a CTH reaction ?

jon · « **Reply #4 on:** June 27, 2012, 04:48:19 PM »

don't get me started on the jews they always infiltrate themselves into government everywhere they go and use thier host nation as muscle to get thier agdenda achieved.
watch, they'll keep the dollar afloat long enough to finance WWIIII then "shalom" Bernanke will pull the plug.

jon · « **Reply #5 on:** June 27, 2012, 08:00:00 PM »

your plan would work just as easily with codiene
i would do this though i would catalytically rearrange 6,7 to the saturated ketonone so then you would have a hyrocodone then you could demethylate it.
the only problem is 48% hbr is to hard on that molecule i tried to demthylate hydrocodone and got tar tried it in acetic acid too got the same results.
if you use the lower concentration of hbr lower temps and an acceleraltor like you suggest it just might work.
and your plan would yeild dihydromorphine.

jon · « **Reply #6 on:** June 28, 2012, 03:03:25 PM »

wy not?

Waggledance · « **Reply #7 on:** July 03, 2012, 07:27:01 AM »

According to the patents mentioned the product should be hydromorphone? And yea it works fine with codeine, already tried that one, similar tar issues to you at first however halving concentration of HBr and reduced temp (as mentioned in original post) solved that problem.

As for getting the Pholcodine out, thats something im working on. Hoping the solubility is similar to codeine so acetone will precip it. However those experiments are yet to come. Otherwise standard basing with ammonium chloride to give precip will be the go i think.

Waggledance · « **Reply #8 on:** July 06, 2012, 10:23:33 AM »

Success!!!

Heres a brief run through.

1) Pholcodine extracted by addition of equimolar (to pholcodine) addition on HCl (dilute solution) to the syrup with stirring. Washed with DCM 3 times then adjusted to pH 9.1 to precipitate Pholcodine freebase a nice crystals.

2) Hydrogenation with RuCl3 in ethanol at 70*C, filtered to remove ruthenium black, pH adjusted to 2.5 then precipitated with ethanol in fridge over night and washed with cold EtOH as per patent.

3) De-morpholination with 25% HBr/Boric acid first at 5*C in ice bath with temp rising to 25*C over 2 hours. Then heated to 40*C for a further 3 hours. pH adjusted to 2.5 then hydromorphone precipitated with ethanol. Filter, wash with cold ethanol. Further recrystallised from ethanol 3 times to give a fine, bleach white powder as the HBr salt.

Initial 1mg sublingual test: Barely noticeable, placebo maybe with a little relaxation

4mg test nasal: Clear activity, small rush with euphoria and relaxation, lasting 1 hour or so

8mg test nasal: Clear activity with nice rush and warmth, good euphoria lasting 3-4 hours

12mg test nasal: This is where ill stay for now, very content!

Obviously this is no use to those in the US however it is applicable to codeine, well known to some however my method with HBr may help some people. To those in the UK and other places where Pholcodine is OTC I highly recommend this. Easy to do and yields a nice product. I plan on going to acetylhydromorphone next after a short holiday and will post a bioassay as I havent seen any experiences for this compound yet.

Waggledance · « **Reply #9 on:** July 07, 2012, 05:48:54 AM »

Was different each time, first was 430mg, second was 505mg and third was 547mg. Will get better as i get the technique down. Its mainly getting the pH right. Look at the pKa of pholcodine, very similar to morphine but slightly different.

You need RuCl3 not Ru black, got it via the interwebs, the chinese are your best friends when it comes to reagents. 1g cost 350 jewnited snakes dollars though. The RuCl3 wasn't a problem as it isn't watched, just expensive! Hydrobromic acid was the hardest to get, luckily I have a good relationship with the local supply store. Easy to synth from Sodium bromide though.

carl_nnabis · « **Reply #10 on:** July 07, 2012, 06:04:14 AM »

(just my offtopic 5 eurocent)

wow... you bought fuckin ruthenium

The price, is it the standard catalogue price from a chemical supplier, it sounds too cheap for it? or is it what the chinese actually want for it?
Ive never bought anything outside the eu (ok i did, but now its EU anyway since the last eu-expansion east

) so i have no experience how cheap the chinese guys actually are in reality, but i can guess its unbeatable cheap since there are no work safety guidelines they have to follow

fresh, if you really need it totally OTC without any chinese involved, even then theres a source for Ru

Some new hard drive types use elemental ruthenium as a very thin layer for something, but i have no knowledge about electronic stuff at all

Waggledance · « **Reply #11 on:** July 07, 2012, 07:16:25 AM »

Haha yea when i comes to chemistry my wallet suffers greatly, i can't resist a beautiful piece of glassware or any item for that matter. Im afraid to address the issue of the $10k rotary evap i just purchased.....hasn't arrived abut im sure ill be happy once it does haha.

Wasn't a catalogue price, just contacted a bunch of suppliers through one of the online directories and took the best price. Indeed the chinese are the cheapest by far and will ship under a false name to avoid expensive chem couriers =D, their glassware is also cheap but not the greatest quality. Heating mantles, stirrers etc are best brought from them aslong as you don't mind a little chinese writing on your equipment.

carl_nnabis · « **Reply #12 on:** July 07, 2012, 07:51:19 AM »

i think i would never even consider to use chinese glassware or equipment in any case, all the old and big labglass manufacturers with a more than 100 year old history are in reach within less than 500km so my glassware is always homecountry quality

wow, a rotovap shipped from oversea? i dont have the nerves to let such a expensive thing after i have bought it just a minute out of my eyes (if i could afford such a thing:P, makes me green jealously

).I wouldt pick it up in person at least from the buyer and transport it myself. But i think in such a wide country this is not really an option, i would just drive less than thirty minutes to a supplier of used laboratory equipment, and could load up everything (every private person with enough money could

) from a complete small scale industrial distillation setup up to HPLC equipment or even some gigantic bioreactor

I have seen for some months ago a custom designed dimroth condenser, which was like the biggest dimroth one has ever seen! two square meter cooling surface, five condenser coils or such, and its former purpose was to fit on a (also custom designed) twenty liter flask!!! Nearly needless to say its price was IIRC 11,999€ which is nearly 15.000 in dollar. The corresponding flask hit the full 20k € off course...
Try to let such an item ship to you, my nerves wont survive it^^

Waggledance · « **Reply #13 on:** July 07, 2012, 09:28:08 AM »

Not shipped from overseas this time, from the home country. Although it is a chinese supplier hahaha, should arrive via courier in a day or two. Glassware from chinese isn't the best idea but their mantles, hotplates etc are fine....actually last longer than some of the 'reputable suppliers' in my experience.

I'd love to get a dimroth condenser, already have a standard leibig, graham and allihn but i do love coiled condensers......so beautiful! O man i love glassware haha. There is a supplier in my country that also has "large" glassware, 20L 3 neck RBFs etc, 2m long condensers, 10L filter flasks and 5L separatory funnels etc etc.....i would kill to have some of it even though i wouldnt use it! Biggest I have use for is 3L in steam distillations. Maybe I should just say 'fuck it' and synth a shit load of MDMA through N-formyl route from MDA originally from Helional? Or I guess if one was smart they could do what people did in the days of safrole and go straight for MDP2P for a one step the desired product, this of course also applies to helional but it would be 2 step to MDMA

. Then i could afford everything I want! Too bad im a paranoid mother f**ker I guess

Author Topic: Pholcodine ----> Hydromorphone, 2-Step (Read 251 times)

Waggledance

Pholcodine ----> Hydromorphone, 2-Step

Balkan Bonehead

Re: Pholcodine ----> Hydromorphone, 2-Step

Waggledance

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Alchemyst

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jon

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jon

Re: Pholcodine ----> Hydromorphone, 2-Step

jon

Re: Pholcodine ----> Hydromorphone, 2-Step

Waggledance

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Waggledance

Re: Pholcodine ----> Hydromorphone, 2-Step

Waggledance

Re: Pholcodine ----> Hydromorphone, 2-Step

carl_nnabis

Re: Pholcodine ----> Hydromorphone, 2-Step

Waggledance

Re: Pholcodine ----> Hydromorphone, 2-Step

carl_nnabis

Re: Pholcodine ----> Hydromorphone, 2-Step

Waggledance

Re: Pholcodine ----> Hydromorphone, 2-Step