looking for Ketamine method from 2-(2-Chlorophenyl)-2-nitrocyclohexanone

[Montecristo]

Hi!
I am looking for a method to produce (s)ketamine from 2-(2-Chlorophenyl)-2-nitrocyclohexanone [CAS 2079878-75-2].
I cannot find much online so maybe a chemist could help?
Thank you!

 

[WillD]

 

[btcboss2022]

View attachment 5208

William DampierI found this but still trying to find the exact amounts of each product :-(

Using zinc powder and formic acid, 2-CPNCH was reduced to norketamine. Through the Eschweiler–Clarke reaction, norketamine was reacted with formaldehyde and formic acid to synthesize ketamine.

 

[btcboss2022]

I found this but still trying to find the exact amounts of each product :-(

View attachment 20699

Using zinc powder and formic acid, 2-CPNCH was reduced to norketamine. Through the Eschweiler–Clarke reaction, norketamine was reacted with formaldehyde and formic acid to synthesize ketamine.

btcboss2022I see your option too for the second step:

Finally, norketamine was converted into ketamine through reductive methylation performed using formaldehyde with sodium cyanoborohydride or sodium triacetoxyborohydride

Could be nice to fix the amounts if possible thanks.

 

[LazZzZz]

I found this but still trying to find the exact amounts of each product :-(

View attachment 20699

Using zinc powder and formic acid, 2-CPNCH was reduced to norketamine. Through the Eschweiler–Clarke reaction, norketamine was reacted with formaldehyde and formic acid to synthesize ketamine.

btcboss2022How do you prevent teriatry amination of the amine group, the dimethylketamine and norketamine are both either too water soluable or too fat soluable respectively and would lead to a large loss in yeild, have you thought about instead refluxing the amine with formic acid to add a formyl group to the amine, protecting the ketone with ethylene glycol, reduction with LAH and a deprotection of the ketal

 

[HerrHaber]

How do you prevent teriatry amination of the amine group, the dimethylketamine and norketamine are both either too water soluable or too fat soluable respectively and would lead to a large loss in yeild, have you thought about instead refluxing the amine with formic acid to add a formyl group to the amine, protecting the ketone with ethylene glycol, reduction with LAH and a deprotection of the ketal

LazZzZzThis is well over the facile area... there must be a more simple way of N monomethylation, NaBH(OAc)3 seems the best.

 

[LazZzZz]

This is well over the facile area... there must be a more simple way of N monomethylation, NaBH(OAc)3 seems the best.

HerrHaberYeilds of 56% leaves something to be desired

 

[JimmyMcGill]

Do you have detailed steps on this method as well?

 

[Montecristo]

thank you, thats a good start. would be very interested to see a write up on this method.

View attachment 5208

William Dampier

 

[WillD]

thank you, thats a good start. would be very interested to see a write up on this method.

thatfellonThe first stage of the reaction will be an excess of zinc and acetic acid with heating. Write in private messages, we will analyze your request. Based on your quantities, experience and equipment.

 

[simplechemistry]

View attachment 5208

William DampierReducing with NaBH4 and oxidising or forming STAB-H in situ will be way more accessible for him. Both high yielding