Thermal rearrangement of Methylketimine to Ketamin

[bbeeasheets]

In step 11 of

https://www.thevespiary.org/rhodium/Rhodium/chemistry/ketamine2.html

undecane is used as a high boiling point solvent I assume. My question is would this reaction be affected by increads pressures? I have a high pressure reaction pot that I would like to use for this step so I can replace the undecane with a cheaper more otc solvent.

[Vaaguh]

If you have a high pressure reactor a good solvent would be acetone for rearanging the hydrochloride salt at 180 °C for 30 minutes.

[yei]

mineral oil boils very high, is made of simple alkanes, and is cheap and OTC.

(shouldn't you be using the freebase?)

[bbeeasheets]

what do you mean by "shouldn't you be using the freebase?"

[yei]

Vaaguh said "using hydrochloride salt", which seems less likely to dissolve in oil than the freebase...

[bbeeasheets]

right. it is the freebase. will acetone dissolve the freebase?

[yei]

acetone is a good, versitile solvent for nonpolars and some polars. However, it boils too low.

Why again did you want to use it? What was wrong with using the best available substitute for decane or whatever, which is mineral oil? I don't think any acetone is required. It will just boil off anyway.

[Rhodium]

Solvent requirements for the ketimine rearrangement:

• High boiling point [High temp is what drives the reaction, so the bp needs to be over 150°C, preferably ~200°C.]
• Reasonably pure [Impurities may degrade your product or impair its isolation. Use a single solvent.]
• Unreactive [Unsuitable types: Haloalkanes, Alkenes, Amines, Acids, Nitriles, Amides, Oxides, etc...]

[Vaaguh]

A great advantage of using a high boiling solvent that also bears a ketone group is that during the rearangement of the ketimine in the hydrochloride form the byproducts that are formed will stay into the solution, this makes it easy for the rearanged ketamine hydrochloride to be filtered off.

(shouldn't you be using the freebase?)

There are a couple of dissadvantages when it comes to rearanging the freebase:

The freebase needs a longer time to rearange compared to the hydrochloride salt which results in more unwanted byproducts.

When a solvent like decahydronaphthalene for example is used when rearanging the ketimine freebase the precipated insoluble tar will make the the extraction of the ketamine using dilute HCl almost impossible.