The optically active amino benzhydrol (I) is acylated with dimethylmalonyl chloride monoethyl ester (II) to yield amide (III). Subsequent reduction of the amide-ester (III) by means of LiAlH4 furnishes amino alcohol (IV). Alternatively, the intermediate amino alcohol (IV) is prepared by reductive alkylation of (I) with 3-hydroxy-2,2-dimethylpropionaldehyde (V) in the presence of NaBH3CN. Condensation of (IV) with fumaryl chloride monoethyl ester (VI) provides amide (VII). Intramolecular cyclization of the conjugated carboxamide (VII) in the presence of K2CO3 leads to the benzoxazepine derivative (VIII). The ethyl ester group of (VIII) is then hydrolyzed under alkaline conditions to furnish acid (IX).
Acid (IX) is coupled to ethyl 4-piperidineacetate (X) by means of diethylphosphoryl cyanide to give amide (XI). The ethyl ester group of (XI) is then hydrolyzed to the corresponding carboxylic acid (XII) employing NaOH in ethanol. Finally, esterification of the alcohol function of (XII) with acetic anhydride in pyridine gives rise to the target acetate ester.