Process for the preparation of nonracemic syn-1-(4-hydroxy-phenyl)-2-(4-hydroxy-4-phenyl -piperidin-1-yl)-1-propanol compounds
AssigneeDsm Catalytica Pharmaceuticals, Inc.
InventorsCharles E. Tucker, Qiongzhong Jiang
Life of this patent
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Abstract
The present invention provides a process for the preparation of a nonracemic diastereomer of 1-(4-benzoxy-phenyl)-2-(4-hydroxy-4-phenyl-piperidin-1-yl)-1-propanol by hydrogenation of a corresponding nonracemic 1-(4-benzoxy-phenyl)-2-(4-hydroxy-4-phenyl-piperidin-1-yl)-1-propanone using a catalyst system comprising ruthenium, a nonracemic diphosphine ligand, a bidentate amine ligand selected from amino-thioethers and achiral diamines, and a base.
Claims20
A process for the preparation of a nonracemic diastereomer selected from 1-(4-hydroxy-phenyl)-2-(4-hydroxy-4-phenyl-piperidin-1-yl)-1-propanol compounds of the structural formula I and stereoisomers thereof,
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- wherein R is selected from hydrogen and hydroxyl protecting groups, comprising hydrogenating a corresponding nonracemic ketone selected from 1-(4-hydroxy-phenyl)-2-(4-hydroxy-4-phenyl-piperidin-1-yl)-1-propanone compounds of the structural formula II and enantiomers thereof,
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- in the presence of a catalyst system comprising ruthenium, a nonracemic diphosphine ligand, a bidentate amine ligand selected from amino-thioethers and achiral diamines, and a base.
A process for the preparation of (1S,2S)-1-(4-benzoxy-phenyl)-2-(4-hydroxy-4-phenyl-piperidin-1-yl)-1- by catalytic hydrogenation of (2S)-1-(4-benzyl-phenyl)-2-(4-hydroxy-4-phenyl-piperidin-1-yl)-1-propanone using a catalyst system comprising ruthenium, a (S,S,S,S)-2,2′-bis-(diarylphosphino)-1,1′-dicyclopentane ligand, a 1,2-phenylene diamine ligand, and a base.
A process for the preparation of (1S,2S)-1-(4-benzoxy-phenyl)-2-(4-hydroxy-4-phenyl-piperidin-1-yl)-1- by catalytic hydrogenation of (2S)-1-(4-benzyl-phenyl)-2-(4-hydroxy-4-phenyl-piperidin-1-yl)-1-propanone using a catalyst system comprising ruthenium, a (S,S,S,S)-2,2′-bis-(diarylphosphino)-1,1′-dicyclopentane ligand, a 2-(alkylthio)aniline ligand, and a base.
Dependencies are inferred from the claim text.