Patent ID: 7737302
Filing Date: 2010-06-15
Classification: C07C

Abstract:
1. A process for preparing bupropion hydrochloride (I), comprising the steps of: (A) obtaining m-chloropropiophenone, bromine, t-butylamine and hydrochloride in the molar ratio of: 1:0.9-1.1:4-10:0.8-1.5; (B) brominating m-chloropropiophenone directly with bromine without addition of a solvent to obtain compound (II), wherein m-chloropropiophenone is firstly heated to a temperature in the range of 50 to 100° C., then bromine is added dropwise to m-chloropropiophenone and reacted with m-chloropropiophenone for 2 to 6 hours at the temperature in the range of 50 to 100° C. to form compound II (m-chloro-α-bromopropiophenone); (C) without purification of the product of said brominating step, aminating compound (II) with t-butylamine to obtain compound (III), wherein t-Butylamine is added to the reaction mixture of bromination and stirred under refluxing for 2 to 6 hours, after removal of redundant t-butylamine, concentrated solution obtained is then extracted by a solution with an organic solvent and water in 5:1-5 mass ratio, organic phase is washed with water and dried with a drying agent to obtain an organic solution of compound III, and (D) reacting compound (III) with hydrogen chloride gas directly to form salt and obtain bupropion hydrochloride (I), which is precipitated and filtered to obtain compound I; (E) crude product of bupropion hydrochloride obtained in step (D) is dissolved in a solvent of ester, alcohol, or mixture of alcohol and water and decolorized with activated carbon which is removed by filtration, the filtrate is cooled to crystallize bupropion hydrochloride which was filtered and dried in vacuum; the drying temperature in vacuum is in the range of 40 to 100° C.; the time for drying may vary from 3 to 8 hours; the vacuum is in the range of −0.04 to −0.09 MPa, wherein the amount of the ester, alcohol or mixture of alcohol and water is 3 to 15 times of the weight of the crude product of bupropion hydrochloride; the said ester is methyl formate, ethyl formate, methyl acetate, ethyl acetate, butyl acetate, ethyl butyrate, said alcohol is methanol, ethanol, propanol, isopropanol, butanol, sec-butanol, isobutanol or tert-butanol; wherein the structure of the compounds I, II and III are: