Parke Davis K derivative

[clubcard]

I seem to remember that I read through all of the papers & patents regarding ketamine in 2011 or 2012. The one thing that stood out was that a patent was given over to a single derivative, to whit the N-ethyl 2-chloro-5-methoxy analogue. It was as the arylcyclohexyamine class was banned so I didn't spend long on it but it just came back to me. I PRESUME that the compound was of particular interest, given that patenting medicines is not cheap...

 

[clubcard]

BTW ring-substitution of the diphenidine class results in toxic compounds. If you want a SIMPLE K analogue, replace the piperidine ring with an N-isopropyl. Since the latter has more potent DRI activity, the subjective effects are much better. I suspect that swapping the 2-phenyl for a 2-p-toluyl moiety will increase DRI activity as well (but is likely too costly). There is a great RT route to making the N-isopropyl analogue. Use isopropylamine hydrochloride and add KOH to freebase AND to remove the water formed when the amine reacts with the ketone.
The imine is almost insoluble in methanol and so can easily be decanted. NaBH4 in alkali conditions simply reduces the imine to an amine. The only downside is that one needs 2500ml of methanol to reduce 340g of imine.

I discovered this trick looking at novel routes used to produce sertraline. Of course, in the case of sertraline, methylamine hydrochloride & KOH are used. I like RT reactions and I quite like using methanol as solvent but I love the use of KOH for 2 purposes. It's über cheap, simple & safe (compared with the majority of organic syntheses). It goes without saying that solvent management is also very simple. From what I have seen, 'meth cooks' are terrible at solvent management and not too bright when it comes to managing a lab. Scary.

 

[sekio]

BTW ring-substitution of the diphenidine class results in toxic compounds.

elaborate? which ring? even metabolically labile groups?

The only downside is that one needs 2500ml of methanol to reduce 340g of imine.

ptc? that is still pretty good when you consider the trivial cost of methanol... can't you buy methylamine in methanol too?

I love the use of KOH for 2 purposes. It's über cheap, simple & safe

methanolic KOH is not what I woulcd call safe... get some of that on your skin or even worse a warm, wet bit of you and you will thoroughly regret it. also it will corrode glass vessels over time. sure it's not t-butyllithium but it's not aqueous bicarb either

 

[fastandbulbous]

elaborate? which ring? even metabolically labile groups?


ptc? that is still pretty good when you consider the trivial cost of methanol... can't you buy methylamine in methanol too?


methanolic KOH is not what I woulcd call safe... get some of that on your skin or even worse a warm, wet bit of you and you will thoroughly regret it. also it will corrode glass vessels over time. sure it's not t-butyllithium but it's not aqueous bicarb either

Methanolic KOH:
Alkaline enough to turn your skin into soap and assorted protein debris, which lets the methanol enter your body transdermally, so you (possibly) end up blind and disfigured. Nasty enough that you don't go anywhere near it without full protective gear and a fume hood...