Ketamine was first synthesized in 1962 in an attempt to find a safer anaesthetic alternative to Phencyclidine (PCP), which was more likely to cause hallucinations and seizures. The drug was first given to American soldiers during the Vietnam War, but today in the developed world its use on humans has been dramatically curtailed because of exaggerated concern about its potential to cause emergence phenomena including out of body experiences in clinical practice. Patients have reported vivid hallucinations, “going into other worlds” or “seeing God” while anaesthetized, and these unwanted psychological side-effects have reduced the use of ketamine in human medicine. However, it is still used widely in veterinary medicine, or as a battlefield anesthetic in developing nations. – Wiki
This is an old text file I had in my archives. I cannot verify the chemistry since I do not produce ketamine nor am I a chemist. This is being posted for educational research purposes only. – drugnerd
Synthesis of Ketamine
To the grignard reagent prepared from 119.0 g of cyclopentyl bromide and 19.4 g of magnesium is added 55.2 g of o-chlorobenzonitrile. The reaction mixture is stirred for three days and thereafter hydrolyzed in the usual manner. From the hydrolysis there is obtained o-chlorophenylcyclopentylketone, bp 96-97°C (0.3 mmHg). To 21.0 g of the ketone is added 10.0 g of bromine in 80 ml of CCl4. 1-bromocyclopentyl-(o-chlorophenyl)-ketone, bp 111-114°C (0.1 mmHg) is isolated in the usual manner. Since it is unstable, it must be used immediately. The bromoketone (29.0g) is dissolved in 50 ml of liquid methylamine freebase. After one hour, the excess liquid methylamine is allowed to evaporate. The organic residue is dissolved in pentane, and upon evaporation of the solvent, 1-hydroxy-cyclopentyl-(o-chlorophenyl)-ketone N-methylimine is isolated, mp 62°C.
1-hydroxycyclopentyl-(o-chlorophenyl)-ketone N-methylimine (2.0 g) is dissolved in 15 ml of decalin and refluxed for 2.5 h. After evaporation of the decalin under reduced pressure, the residue is extracted with dilute hydrochloric acid, the solution treated with decolorizing charcoal, and the resulting acidic solution is made basic. The liberated product, 2-methylamino-2-(o-chlorophenyl)-cyclohexanone (Ketamine), after recrystallization from pentane-ether, has a mp of 92-93°C. The hydrochloride has a mp of 262-263°C.