31677-93-7

A convenient, scalable, and commercially viable process for the production of the antidepressant drug bupropion hydrochloride (1) is reported. The process relies upon an improved, large-scale synthesis of the key intermediate, m-chloro-bromopropiophenone (4). During process development, bromine was replaced with N-bromosuccinimide (NBS) in the presence of para-toluene sulfonic acid (p-TSA), for the bromination of m-chloropropiophenone (3), in either a very low volume of acetonitrile or under solvent-free conditions, to furnish 4. Intermediate 4 was further reacted with t-butylamine in N-methyl-2-pyrrolidinone (NMP) to afford bupropion free base (5), followed by treatment with a saturated solution of hydrochloric acid in isopropyl alcohol (IPA-HCl) to afford bupropion hydrochloride (1). This improved process provides pure bupropion hydrochloride (1) in good yields and at considerably lower cost than existing processes, and it does not involve the use of hazardous reagents. Copyright

A new and practical method has been developed for the transformation of racemic α-bromo ketones to chiral α-azido and α-amino ketones with high enantioselectivity using phase transfer, ion-pair mediated reactions with a recoverable chiral quaternary salt (10 mol %) as catalyst in fluorobenzene-water. The process has been generalized to a variety of other attachments including of C, O, S, and NHR.

The invention discloses a preparation method of bupropion hydrochloride. M-chlorophenylacetone is used as a raw material to take bromination reaction with sodium bromide, sulfuric acid and hydrogen peroxide in a water-halohydrocarbon solvent to prepare a brominated intermediate; then the prepared bromide reacts with tert-butylamine to prepare amfebutamone, after the reaction for preparing amfebutamone is completely reacted, the water is directly added, after a reaction solution is layered, the layered organic layer is cleaned and distilled to obtain amfebutamone, and obtained amfebutamone is acidified by virtue of isopropanol hydrochloride to obtain bupropion hydrochloride; and the peparation process of amfebutamone, the alkalinity of a water layer obtained after the layering of the reaction solution is adjusted by using sodium hydroxide, after tert-butylamine is recovered in a distillation manner, the water layer comprising bromine ions is concentrated, the pH value is adjusted to beneutral by using sulfuric acid, the obtained aqueous solution comprising sodium bromide is used for taking the bromination reaction again so as to be circularly utilized. By adopting the preparation method, the environment-friendly circular utilization of bromine is realized, and the production cost is reduced.

The invention discloses a novel method for preparing bupropion hydrochloride. According to the invention, m-chlorophenylacetone is taken as an initiator, then is brominated in a hydrobromic acid-hydrogen peroxide system, 3'-chlorine-alpha-bromophenyl ethyl ketone is synthesized; then through replacement by tert-butylamine and acidification by HCl-absolute ethyl alcohol, bupropion hydrochloride is obtained. The preparation method of bupropion hydrochloride replaces traditional bromine bromination, pollution can be effectively reduced, damage due to bromine volatilization on the operators can be greatly mitigated, and the method has the advantages of simple operation, low cost, high yield, and less side reaction, and is very suitable for industrial production.

Compositions and methods are disclosed using a purified (R)(-) enantiomer of bupropion to treat central nervous system disorders with fewer side effects compared to those seen in subjects treated with racemic bupropion. Additionally disclosed are methods and intermediates for producing enantiomerically purified (R)(-) bupropion, stable pharmaceutical formulations of (R)(-) bupropion, and pharmaceutical products and kits comprising (R)(-) bupropion for clinical use.

The present invention relates to new phenylpropanone modulators of dopamine receptors, serotonin receptors, and/or nicotinic acetylcholine receptors, pharmaceutical compositions thereof, and methods of use thereof.

The present invention is directed to novel codrugs comprising bupropion or hydroxybupropion and an opioid antagonist or an opioid agonist joined together by chemical bonding. The codrugs provide a significant increase in the transdermal flux across human skin, as compared to the basic opioid antagonist or opioid agonist.

This invention described a synthesis method of bupropion hydrochloride. m-chloropropiophenone was brominated directly with bromine, then aminated with t-butylamine and finally reacted with HCl to obtain crude product of bupropion hydrochloride. Pure product was obtained after recrystallization. This method is convenient and suitable for commercial manufacturing because of low cost of production, high yield, less byproducts and being environmental friendly.

The present invention relates to an improved process for preparing Bupropion Hydrochloride of formula (I). The present invention also provides a process for purification of Bupropion hydrochloride.

Process for crystallising Bupropion hydrochloride comprising the following stages: a) Bupropion hydrochloride is dissolved in a mixture comprising methanol and a precipitating solvent for Bupropion hydrochloride; b) any insoluble residue is removed; c) th

This invention is related to the preparation of bupropion hydrochloride. The reaction of 3'-chloropropiophenone with bromine in presence of tert-butylamine to prepare the bupropion free base and then recovering of bupropion hydrochloride by the addition of hydrochloric acid is described.