Method for preparing of L-phenylephrine hydrochloride
AssigneeBoehringer Ingelheim Pharma GmbH & Co. KG
InventorsFranz Dietrich Klinger, Lienhard Wolter, Wolfgang Dietrich
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Abstract
The present invention relates to an improved process for preparing L-phenylephrine hydrochloride 3 on an industrial scale by asymmetric hydrogenation as the key step and a special sequence of subsequent steps, using [Rh(COD)Cl]2 as catalyst and a chiral, two-pronged phosphine ligand such as (2R,4R)-4-(dicyclohexylphosphino)-2-(diphenylphosphino-methyl)-N-methyl-aminocarbonyl-pyrrolidine as the catalyst system.
Claims22
A process for preparing L-phenylephrine hydrochloride from prochiral N-benzyl-N-methyl-2-amino-m-hydroxyacetophenone hydrochloride, the process comprising:
- (a) asymmetrically hydrogenating prochiral N-benzyl-N-methyl-2-amino-m-hydroxyacetophenone hydrochloride using a catalyst system comprising [Rh(COD)Cl]2 and a chiral, bidentate phosphine ligand, to obtain N-benzyl-L-phenylephrine;
- and
- (b) reductively debenzylating the N-benzyl-L-phenylephrine obtained from step (a) using palladium and hydrogen, to obtain L-phenylephrine hydrochloride,
- wherein the molar ration of N-benzyl-N-methyl-2-amino-m-hydroxyacetophenone hydrochloride to [Rh(COD)Cl]2 is between 5000:1 and 100,000:1.
Dependencies are inferred from the claim text.