Ketamine synthesis
- Thread starter G.Patton
- Start date
You can substitute decalin by cyclohexane, probably
- By OrgUnikum
Cyclohexane has a boiling point of 81 °C what would mean the thermal rearrangement would need 7 to 10 days at reflux. But then one could use IPA, same bp and it is known to work from literature (7 to 10 days at reflux).
Ethylbenzoate works.
Ethylene Glycol is another solvent which works and of better availability.
The yield is never near to quantitative, actually when using the Ketimine as base yields suffer, for decent yields the HCl salt must be used. It must also be done under strictly anhydrous conditions or yields suck. (the Imine will hydrolyze back to MeNH2, unsurprisingly regarding the rigorous conditions).
The rearrangement is catalyzed by Lewis Acids, MgCl2 And AlCl3 (anhydrous) work well. 0,1 mol equivalent are needed but AlCl3 can also take care of any water still present, the amount used must be adjusted of course, say X g needed to scavenge the water plus 0,1 mol to catalyze the reaction.
The use of AlCl3 reduces the temperature needed to ~130 °C (to take the same time as 180 °C would take un-catalyzed).
Another tip: Stay away from CCl4 the stuff is not just toxic but its mean and hard to get for good reasons. Gladly it is completely unnecessary for brominating the alpha position. The foolproof way to do this is by using CuBr2 what does the job quantitativly and without side-reactions.
For reaction conditions just Google "Bromination with CuBr2" and you will quickly find the standard conditions for this described and those work perfectly well in this case.
Ethylbenzoate works.
Ethylene Glycol is another solvent which works and of better availability.
The yield is never near to quantitative, actually when using the Ketimine as base yields suffer, for decent yields the HCl salt must be used. It must also be done under strictly anhydrous conditions or yields suck. (the Imine will hydrolyze back to MeNH2, unsurprisingly regarding the rigorous conditions).
The rearrangement is catalyzed by Lewis Acids, MgCl2 And AlCl3 (anhydrous) work well. 0,1 mol equivalent are needed but AlCl3 can also take care of any water still present, the amount used must be adjusted of course, say X g needed to scavenge the water plus 0,1 mol to catalyze the reaction.
The use of AlCl3 reduces the temperature needed to ~130 °C (to take the same time as 180 °C would take un-catalyzed).
Another tip: Stay away from CCl4 the stuff is not just toxic but its mean and hard to get for good reasons. Gladly it is completely unnecessary for brominating the alpha position. The foolproof way to do this is by using CuBr2 what does the job quantitativly and without side-reactions.
For reaction conditions just Google "Bromination with CuBr2" and you will quickly find the standard conditions for this described and those work perfectly well in this case.
It is need to get free base of Ketamine. If you want to get Ketamine salt, you don't need basify this product-contain solution.
11. Ketamine
10 g of methylketimine is dissolved in 100 mls undecane and boiled at 195 °C for 3-4 hrs. Ketamine is extracted with 20% HCl. Acidic extract is basified and extracted with DCM. Solvent is removed, giving the product as an oil that quickly crystallizes. It can be purified by recrystallization from pentane/ether or hexane/ether. The yields are close to quantitative.
What is written here?
10 g of methylketimine is dissolved in 100 mls undecane and boiled at 195 °C for 3-4 hrs. Ketamine is extracted with 20% HCl. Acidic extract is basified and extracted with DCM. Solvent is removed, giving the product as an oil that quickly crystallizes. It can be purified by recrystallization from pentane/ether or hexane/ether. The yields are close to quantitative.
What is written here?
It is simple acid/base extraction. Please, read several times topic Extraction, if you don't understand process. There is video explanation. You have to make acid space there, extract with ether (75 ml). Then, basify mixture and extract again (75 ml).
No, in the top organic layer
Yes, you have to stir this reaction too without heating.
What do you mean?
Yes, you have to stir this reaction too without heating.
What do you mean?
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NEW VIDEO
MDA Synthesis. Part 1 of 3.