A process for the preparation of O-desmethylvenlafaxine (ODV, II), or a pharmaceutically acceptable salt thereof is disclosed, which comprises reacting venlafaxine, or a salt thereof, with a thiol reagent, wherein the thiol reagent is a dithiol, an aminothiolate anion, an aminothiol, or an inorganic thiol. Preferably, the aliphatic dithiol is 1,2-ethane dithiol the aminothiolate anion or aminothiol is an N,N-dialkylaminoalkane thiol and most preferably, 2-diethylaminoethane thiol, Et2N-CH2CH2-SH and the inorganic thiol is sodium thiol. Said reaction is preferably carried out in the presence of a reaction solvent selected from an alcohol such as 1-butanol, polyethylene glycol, methyl cellosolve and ethyl cellosolve, and wherein a thiolate anion is generated by treatment of the thiol reagent with a base (preferably, potassium t-butoxide) in the reaction solvent.
