SYNTHESIS OF 3-4-(1,1-DIMETHYL-PROPYL)-PHENYL-2-METHYL-PROPIONALDEHYDE AND cis-4--2,6-DIMETHYL-MORPHOLINE (AMOROLFINE)

摘要

3-[4-(1,1-Dimethyl-propyl)-phenyl]-2-methyl-propionaldehyde and cis-4-{3-[4-(1,1-dimethyl-propyl)-phenyl]-2-methyl-propyl}-2,6-dimethyl-morpholine (Amorolfine) are synthesized, first by Heck reacting a compound of general formula (VI):; ;with 2-methyl-prop-2-en-1-ol of formula (VII):; ;in the presence of a palladium catalyst and a base, in a solvent selected from among N,N-dimethylformamide, polar protic and non-polar organic solvents, and at a temperature ranging from 60° C. to 150° C., and then conducting an amino reduction by reacting the 3-[4-(1,1-dimethyl-propyl)-phenyl]-2-methyl-propionaldehyde of formula (II) with cis-2,6-dimethyl morpholine of formula (IV):; ;in the presence of a reducing agent and in a solvent.