Synthesis of 2-(2-Fluorophenyl)-2-methylamino-Cyclohexanone as a New Ketamine Derivative

Abstract

The main goal of this article is to the present research on the development of ketamine derivatives. The target molecule was a fluoroderivative of ketamine, for which a multistep synthesis has been reported. This novel ketamine derivative, 2-(2-fluorophenyl)-2-methylamino-cyclohexanone, has been called fluoroketamine by our research group. The starting fluorobenzonitrile was reacted with the appropriate Grignard reagent followed by the bromination reaction to obtain α-bromocyclopentyl-(2-fluorophenyl)-ketone. The reaction of the obtained ketone with methylamine at −40 °C then resulted in the formation of α-hydroxycyclopentyl-(2-flourophenyl)-N-methylamine. Finally, the five-memberd ring cyclopentanol was expanded to the cyclohexylketone by a thermal rearrangement reaction. The HCl salt of the target molecule, which is soluble in water, was obtained by the acidification of the free fluoroketamine with HCl. Preliminary animal tests on mice have shown that the resulting fluoroketamine has some advantages over ketamine in terms of the effective dose and the recovery time.

GRAPHICAL ABSTRACT

Keywords:

• Anesthesia
• bromination
• Grignard reaction
• ketamine
• ring expansion

Notes

^a Isolated yield.

^a Isolated yield.