合成路线1

The esterification of 3-benzoylpropionic acid (I) with methanol and sulfuric acid gives the corresponding methyl ester (II), which is regioselectively reduced with (-)-B-chlorodiisopinocampheylborane [(-)-DIP-Cl] in THF, yielding the chiral lactone (III). Ring opening of (III) with ammonia in methanol affords the chiral butyramide (IV), which is treated with iodobenzene diacetate (IBA) in acetonitrile to provide the cyclic carbamate (V). The methylation of (V) with NaH and methyl iodide in DMF gives the expected N-methyl derivative (VI), which is hydrolyzed with NaOH in refluxing ethanol to yield the chiral 3-(methylamino)-1(S)-phenyl-1-propanol (VII). Finally, this compound is condensed with 4-(trifluoromethyl)chlorobenzene (VIII) by means of NaH in DMSO. The intermediate propanol (VII) can also be obtained directly from (V), by reductive cleavage of the carbamate ring with borane/dimethyl sulfide complex in THF.