合成路线1

Reaction of methyl 4-hydroxybenzoate (XI) with difluorochloromethane and potassium tert-butoxide provided difluoromethyl ether (XII). After basic hydrolysis of the methyl ester of (XII), the resulting carboxylic acid (XIII) was converted to acid chloride (XIV) by means of refluxing SOCl2. Subsequent coupling of (XIV) with benzyl bromide in the presence of Zn and palladium catalyst produced the diaryl ethanone (XV). Reductive amination of (XV) with ammonium formate at 160 C gave formamide (XVI), which was hydrolyzed to racemic amine (XVII) with boiling HCl. Alkylation of this amine with the intermediate iodide (X) in THF at 110 C in a sealed flask yielded a diastereomeric mixture of secondary amines (XVIII), which were separated by column chromatography. The required (R,R)-isomer was desilylated employing tetrabutylammonium fluoride and AcOH to produce aminoalcohol (XIX). Finally, hydrogenolytic cleavage of the benzyl ether of (XIX) furnished the title compound.