Stereoselective Synthesis of Diltiazem via Dynamic Kinetic Resolution
ABSTRACT An efficient synthesis of diltiazem has been developed using dynamic kinetic resolution (DKR) as a key step. The methyl (2S,3S)-2-chloro-3-hydroxy-3-(4-methoxyphenyl)propionate was synthesized from a racemic mixture of α-chloro-β-keto ester, with high ANTI diastereoselectivity (92%) and ena...
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Veröffentlicht in: | Synthesis (Stuttgart) 2003-10, Vol.2003 (15), p.2405-2409 |
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Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Online-Zugang: | Volltext |
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Zusammenfassung: | ABSTRACT
An efficient synthesis of diltiazem has been developed using dynamic kinetic resolution (DKR) as a key step. The methyl (2S,3S)-2-chloro-3-hydroxy-3-(4-methoxyphenyl)propionate was synthesized from a racemic mixture of α-chloro-β-keto ester, with high ANTI diastereoselectivity (92%) and enantioselectivity (95%), based on an asymmetric hydrogenation reaction with a chiral ruthenium(II) catalyst, simply prepared by mixing Ru(cod)(2-methylallyl)
2
with the atropisomeric ligand (S)-MeO-BIPHEP. By treatment of this α-chloro-β-hydroxy ester with a base, the corresponding TRANS methyl glycidate, a key intermediate of diltiazem, was easily obtained. |
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ISSN: | 0039-7881 1437-210X |
DOI: | 10.1055/s-2003-42397 |