Synthesis of Desmethylvenlafaxine

OBJECTIVE To synthesize O-desmethylvenlafaxine. METHODS Desmethylvenlafaxine was synthesized from p-hydroxylphenylacetic acid via etherification, chlorination and amination to give N, N-dimethyl-4-benzyloxy phenylacetamide (5), which was subjected to condensation with cyclohexanone in the presence of n-BuLi to give 1-(4-benzyloxyphenyl)-dimethylaminocarbonylmethyl cyclohexanol (6), and then followed by reduction using BH3/THF and hydrogenolysis with Pd/C to give desmethylvenlafaxine (1). RESULTS The total yield of O-desmethylvenlafaxine was 28.8%, and its structure was confirmed by EA, 1H-NMR, MS and IR. CONCLUSION The synthetic route for O-desmethylvenlafaxine is convenient for industrial manufacture with high yield and good purity.