合成路线1

Reaction of 3-(tetrahydropyranyloxy)benzaldehyde (I) with acetonitrile (II) in the presence of t-BuOK in THF gives the b-hydroxypropionitrile (III), which by reduction with LiAlH4 in THF/Et2O yields the primary amine (IV). N-Protection of amine (IV) with ethyl trifluoroacetate (V) in THF affords the carbamate (VI), whose secondary hydroxyl group is oxidized with MnO2 in CH2Cl2 to yield the ketone (VII). Enantioselective reduction of ketone (VII) with (–)-DIP-Cl and DIEA in THF provides the (R)-alcohol (VIII), which is O-alkylated at its phenolic hydroxyl group with cyclohexylmethyl bromide (IX) and K2CO3 in DMF to give ether (X). Finally, compound (X) is N-deprotected by means of K2CO3 in MeOH/H2O and treated with HCl in i-PrOH .