Process for preparing (R)-salbutamol
AssigneeBoehringer Ingelheim Pharma GmbH & Co. KG
InventorsPaul Kreye, Alfons Lenhart, Franz Dietrich Klingler
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Abstract
Disclosed are processes for preparing levosalbutamol or the pharmacologically acceptable salts thereof on an industrial scale, using asymmetric hydrogenation as the key step and optionally a special sequence of subsequent steps, using rhodium as catalyst and a chiral bidentate phosphine ligand such as (2R, 4R)-4-(dicyclohexylphosphino)-2-(diphenyl-phosphino-methyl)-N-methyl-aminocarbonyl-pyrrolidine as catalyst system.
Claims25
A process for preparing levosalbutamol or a pharmacologically acceptable salt thereof from prochiral salbutamone, comprising subjecting the salbutamone to asymmetric hydrogenation in the presence of rhodium and a chiral bidentate phosphine ligand as catalyst system and in the presence of a solvent comprising a protic or aprotic solvent, to obtain levosalbutamol, and optionally converting the resulting levosalbutamol into a salt with an acid.
A process for preparing levosalbutamol or a pharmacologically acceptable salt thereof, comprising:
- (a) brominating 4-acetyloxy-3-acetyloxymethylbenzophenone,
- (b) reacting the product obtained with N-tert-butyl-N-benzylamine to obtain N-benzylsalbutamone,
- (c) hydrogenating the N-benzylsalbutamone obtained in the presence of a palladium catalyst to obtain salbutamone,
- (d) hydrogenating the salbutamone obtained in the presence of rhodium and a chiral bidentate phosphine ligand and in the presence of a solvent comprising a protic or aprotic solvent, to obtain levosalbutamol, and
- (e) optionally treating the obtained levosalbutamol it with an acid to obtain a salt thereof.
Dependencies are inferred from the claim text.