robojunkie
08-06-2009, 07:32 AM
Imagine this, our friend oxycodone, potency around morphine, can be made three orders of magnitude stronger in a few easy steps.
1. Oxycodone, reacted with ethylene glycol and TsCl at reflux with water trap can give a "ketal", as in C=O becomes C-O-CH2-CH2-O-Back to first C to protect from base in step 2.
2. OC-ketal is reacted with NaH or similar base to remove 14-OH proton in DMF and reacted with cinnamyl bromide (Phenyl-CH=CH-CH2-Br) to give 14-cinnamyl-OC-ketal.
3. Then the activated double bond can be easily reduced at around 2 atmospheres in HOAc/some metal to give 14-Phenylpropoxy-OC-ketal.
4. Finally, and easily, the last stuff could be boiled in conc. HBr which would then hydrolyze the ketal back to C=O and for added potency it (main reason for conc. HBr, not necessary to hydrolyze ketal, weaker wet acid will do it) will O-demethylate via Sn2 the aryl methyl ether to give one 14-phenylpropoxy-dihydromorphinone. In other words this is essentially oxymorphone/opana with a phenylpropyl group attached to the 14 hydroxy (which is the difference between oxycod/morph and hydrocod/morph). Most importantly, and I suppose academically as NO one should really bother with this, especially when one can just start at step 4 with OC and get opana in about an hour, is that the 14-phenylpropoxydihydromorphone is more than 1000x stronger than morphine, or over 10 times stronger than my old friend fentanyl, in fact were one to draw out the structures three dimensionally, one can see why this phenylpropyl group addition would have such an effect when drawn next to fentanyl and etorphine as well as the enkephalins and drawn in a way that the freely rotating bonds are spatially similar.
This procedure isn't something I've done nor do I plan on it, but it has been done in literature and patents and is likely something that some aspiring chemistrevolutionary could try other than fentanyl (as I am in long term retirement, at least until my daughter grows up, free of the need for opiates) who has some skill. I've read this stuff and it is significantly easier than my fentanyl synthesis but is obviously dangerous to any cavalier chemist on the last step and could NEVER EVER be cut or used to profit without being party to manslaughter because it is too potent to cut, it could only ever be freely distributed in standardized ampules or vials in incredibly dilute solutions with buffers and so forth to block any smartass from thinking they can easily evap it or acid/base it out.
Disclaimer: I really haven't done this nor do I plan on it, its just there for informational purposes as I have seen this compound or a similar one discussed here before. It would be very dangerous for anyone I know here other than me to try it, quite possibly lethal and as such this is why the reference and specifics aren't given. It really is for curiosity factor only. Wannabe Bentleys/Janssens/Shulgins/Strikes/Highsmiths/etcs, you are forewarned.
1. Oxycodone, reacted with ethylene glycol and TsCl at reflux with water trap can give a "ketal", as in C=O becomes C-O-CH2-CH2-O-Back to first C to protect from base in step 2.
2. OC-ketal is reacted with NaH or similar base to remove 14-OH proton in DMF and reacted with cinnamyl bromide (Phenyl-CH=CH-CH2-Br) to give 14-cinnamyl-OC-ketal.
3. Then the activated double bond can be easily reduced at around 2 atmospheres in HOAc/some metal to give 14-Phenylpropoxy-OC-ketal.
4. Finally, and easily, the last stuff could be boiled in conc. HBr which would then hydrolyze the ketal back to C=O and for added potency it (main reason for conc. HBr, not necessary to hydrolyze ketal, weaker wet acid will do it) will O-demethylate via Sn2 the aryl methyl ether to give one 14-phenylpropoxy-dihydromorphinone. In other words this is essentially oxymorphone/opana with a phenylpropyl group attached to the 14 hydroxy (which is the difference between oxycod/morph and hydrocod/morph). Most importantly, and I suppose academically as NO one should really bother with this, especially when one can just start at step 4 with OC and get opana in about an hour, is that the 14-phenylpropoxydihydromorphone is more than 1000x stronger than morphine, or over 10 times stronger than my old friend fentanyl, in fact were one to draw out the structures three dimensionally, one can see why this phenylpropyl group addition would have such an effect when drawn next to fentanyl and etorphine as well as the enkephalins and drawn in a way that the freely rotating bonds are spatially similar.
This procedure isn't something I've done nor do I plan on it, but it has been done in literature and patents and is likely something that some aspiring chemistrevolutionary could try other than fentanyl (as I am in long term retirement, at least until my daughter grows up, free of the need for opiates) who has some skill. I've read this stuff and it is significantly easier than my fentanyl synthesis but is obviously dangerous to any cavalier chemist on the last step and could NEVER EVER be cut or used to profit without being party to manslaughter because it is too potent to cut, it could only ever be freely distributed in standardized ampules or vials in incredibly dilute solutions with buffers and so forth to block any smartass from thinking they can easily evap it or acid/base it out.
Disclaimer: I really haven't done this nor do I plan on it, its just there for informational purposes as I have seen this compound or a similar one discussed here before. It would be very dangerous for anyone I know here other than me to try it, quite possibly lethal and as such this is why the reference and specifics aren't given. It really is for curiosity factor only. Wannabe Bentleys/Janssens/Shulgins/Strikes/Highsmiths/etcs, you are forewarned.