Kilogram synthesis of (R)-(-)-denopamine by Ir/f-amphox catalyzed asymmetric hydrogenation

Abstract

A practical and efficient two-step synthetic process for the preparation of (R)-(-)-denopamine has been developed. The key step asymmetric hydrogenation was conducted at mild temperature (60 ​°C) under a hydrogen pressure of 50 ​atm by using Ir/f-amphox as catalyst at low catalyst loading (S/C ​= ​20 ​000). Under the optimized condition, the desired product (R)-(-)-denopamine was obtained with 70% total yield and > 99.9% ee after crystallization. The pilot-scale experiment has been performed at 500 ​g level, showing great potential for the production of high quality active pharmaceutical ingredient (API).

Keywords

• (R)-Denopamine
• Asymmetric hydrogenation
• f-Amphox
• Practical process