Trapencaine is prepared from 3-(n-pentyloxy)phenylisocyanate and (+)-trans-2-(1-pyrrolidinyl)cyclohexanol in dry benzene or some other inert solvent. Stereochemically pure isomer is obtained by treatment of the pure base with hydrochloric acid, yielding the corresponding salt.
By refluxing a solution of equimolecular quantities of 3-pentyloxyphenyl isocyanate (I) and trans-2-(1-pyrrolidinyl)cyclohexanol (II) in toluene. The obtained pentacaine base is transformed to the hydrochloride by treatment of an ether solution of anhydrous hydrogen chloride (1,2). The starting amino-alcohol (II) is prepared from cyclohexanol (III), which is first dehydrated to cyclohexene (IV). The following addition of HClO gives trans-2-chlorocyclohexanol (V), which, in turn is dehydrochlorinated to 1,2-epoxycyclohexane (VI). Final addition of pyrrolidine (A) yields the required intermediate (II).