(CAS NO.: ), with other name of (R)-(-)-N-Methyl-gamma-(2-methylphenoxy)benzenepropanamine hydrochloride, could be produced through the following synthetic methods.

Method one:

The asymmetric epoxidation of (E)-3-phenyl-2-propen-1-ol (I) by means of titanium tetraisopropoxide, (+)-diethyl tartrate (+)-(DET) and tBu-OOH in dichloromethane gives the chiral epoxide (II), which is opened by means of bis(2-methoxyethoxy)aluminum hydride (Red-Al) in DME to yield the chiral diol (III). The regioselective reaction of (III) with Ms-Cl and TEA in ethyl ether affords the primary mesylate (IV), which is condensed with 2-methylphenol (V) by means of PPh₃ and DEAD in ethyl ether to provide the adduct (VI). Finally this compound is treated with methylamine in hot aq. THF to give rise to the target (R)-tomoxetine.

Method two:

The reduction of omega-chloropropiophenone (I) with NaBH₄ in ethanol gives 3-chloro-1-phenyl-1-propanol (II), which is treated with butyric anhydride and pyridine in dichloromethane to yield the corresponding racemic ester (III). The optical resolution of (III) with immobilized lipase B from Candida antarctica (CALB) affords a mixture of unreacted (S)-ester and (R)-alcohol (IV) that are separated by column chromatography. Condensation of th (R)-alcohol (IV) with 2-methylphenol (V) by means of PPh₃ and diethyl azodicarboxylate (DEAD) in THF gives the corresponding ether (VI), which is finally treated with methylamine in refluxing ethanol.