Sulfuric Acid → Neramexane

Participants

Reaction Steps

To a vigorously stirred solution of 1-hydroxy-1,3,3,5,5-pentamethylcyclohexane (3.4 g; 20 mmol) and trimethylsilyl cyanide (2.58 g; 26 mmol; 1.3 eq.) in ethyl acetate (4 ml), 95% sulfuric acid (3.2 ml; 60 mmol; 3.1 eq) are added during 1 hour keeping the temperature at −10° C. for 15 min, and then allowing the mixture to reach ambient temperature. After stirring at ambient temperature for 15 hours, the mixture is diluted with 20 ml ice water. Subsequently, the mixture is refluxed with stirring for 10 hours, cooled to ambient temperature, diluted with 40 ml water and 20 ml ether and neutralized with 20% aqueous sodium hydroxide until a pH of 10. The organic phase is separated and dried. Dry hydrogen chloride is passed through the solution until the ether becomes acidic. Solvent is removed and the residue is washed with ether to give 3.1 g Neramexane in the form of its hydrochloride.

Provenance & Evidence