METHOD OF PREPARING DESVENLAFAXINE AND ITS SALTS

摘要

A method for the preparation of 4-(2-(dimethylamino)-l-(l-hydroxycyclohexyl)ethyl) phenol of formula (I), known under generic name desvenlafaxine, and its pharmaceutically acceptable salts, which comprises (a) mixing of the starting material O-benzyldesvenlafaxine or its derivative of formula (II), wherein R is H, 4-methyl, 4-methoxy, 3,4-dimethoxy, 2-nitro, 4-nitro, 4-chloro, 4- bromo, 2,6-dichloro or 2,6-difluoro, in an organic solvent or a mixture of solvents, and subsequent dissolving of the starting material by decreasing the pH to a value of 3 to 8 by addition of an inorganic or organic acid, or dissolving of O-benzyldesvenlafaxine or its derivative of formula (II) in an organic solvent or a mixture of solvents, wherein the compound of formula (II) is in the form of a salt with an inorganic or organic acid and the pH of the solution has a value of 3 to 8, (b) converting O-benzyldesvenlafaxine or its derivative of formula (II) to desvenlafaxine I by catalytic hydrogenation on a Raney catalyst, (c) removing the catalyst from the desvenlafaxine solution by filtration and subsequent increasing the pH to a value of 8 to 11 by addition of an inorganic or organic base, (d) isolating the desvenlafaxine base I by filtration, (e) converting the desvenlafaxine base I to a pharmaceutically acceptable salt. Formulae (I), (II)