Amino Ketone Rearrangements. VII.¹ Synthesis of 2-Methylamino-2-Substituted Phenylcyclohexanones

Synthesis and N-Methyl-d-aspartate (NMDA) Receptor Activity of Ketamine Metabolites

“…Thus, a modification of the original synthetic route for ketamine, followed by a chiral resolution, was utilized. 10 Starting from commercially available ketone 12 , bromination of the cyclopentyl ketone, followed by condensation with concentrated ammonium hydroxide, gave imine 14 . 11 Use of microwave irradiation to accomplish the thermal rearrangement 10 gave racemic norketamine ( 2 ) in 44% overall yield from commercial materials on gram scale without chromatographic purification.…”

Improved Methods for Thermal Rearrangement of Alicyclic α-Hydroxyimines to α-Aminoketones: Synthesis of Ketamine Analogues as Antisepsis Candidates

“…This type of thermal rearrangement has been studied for almost half century first by Stevens [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ] and later on by Compain [ 27 , 28 , 29 , 30 ], however the conditions needed for the reactions were not improved in those works. Interestingly, our starting compounds 4[a–g] , 5[a–g] for the thermal rearrangement were hypothesized (but not isolated) by Stevens (see Figure 2 , Figure 4 and Figure 5 ) as being the intermediates between the starting five member ring A and the product six member ring C isomers in his studies.…”

“… Hypothetical model (according to Stevens [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]) for inter-conversion between A, C and D by a thermal rearrangement. …”

Syntheses of Ketamine and Related Analogues: A Mini Review

“…A series of papers were published which detail kinetic studies of the amino ketone rearrangement, and laid the foundation for the synthesis of ketamine-like compounds. [22][23][24][25][26] During this period, ketamine emerged as a safer anaesthetic than PCP, which was also synthesised by Parke-Davis. In 1964 human trials carried out by Dr. Edward Domino of the Department of Pharmacology and Dr. Guenter Corssen of the Department of Anaesthesiology at the University of Michigan found that ketamine is well tolerated by patients, producing rapid anaesthesia and analgesia with minimal side effect compared to PCP, but for a shorter duration of time.…”