Ketamine metabolism: identification and synthesis of a deaminated product

During attempts to synthesize 2-amino-2-(2-chlorophenyl)-6-hydroxycyclohexanone (6), a ketamine metabolite, an unexpected product, 3-(2-chlorophenyl)-2-hydroxy-2-cyclohexenone (4) was obtained as the major product. This compound apparently was formed by rearrangement and deamination of 6 during the isolation and purification procedures. This same compound was found in plasma and urine extracts obtained from mice and rats that had been treated with either ketamine or norketamine. It is suggested that 3-(2-chlorophenyl)-2-hydroxy-2-cyclohexenone (4), isolated from these biological samples, probably arose from decomposition of the 6-hydroxylated metabolite of ketamine or norketamine and is itself not a true metabolite.