Lewis Acid-Catalyzed Racemization and Recycling of the Undesired (R)-Ketamine,Organic Process Research & Development

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Lewis Acid-Catalyzed Racemization and Recycling of the Undesired (R)-Ketamine
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2020-01-14 , DOI: 10.1021/acs.oprd.9b00436
Shenghua Gao ₁ , Xuezhi Gao ₁ , Houyong Li ₂ , Anjiang Yang ₁ , Zhezhou Yang ₁ , Fuli Zhang ₁

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The first detailed description of the Lewis acid-catalyzed racemization of (R)-ketamine is reported. A process for racemization of the undesired (R)-ketamine enantiomer produced from the resolution for preparing the NMDA receptor antagonist (S)-ketamine was developed in quantitative yield with 99% chemical purity in the presence of a Lewis acid at 150 °C. Varying degrees of racemization were observed in the presence of various frequently used Lewis acids separately, and the catalytic efficiencies were arranged as follows: MgCl₂ ≈ AlCl₃ > FeCl₃ > ZnCl₂ > BF₃ > CaCl₂. The racemized ketamine was subsequently resolved using l-(+)-tartaric acid to obtain (S)-ketamine in 41% yield with 99.5% ee. Such a concise and cost-efficient approach for the racemization can be industrially useful to recycle the waste (R)-ketamine enantiomer into the resolution process to obtain (S)-ketamine.

中文翻译：

路易斯酸催化的外消旋和不需要的（R）-氯胺酮的回收

报道了路易斯酸催化的（R）-氯胺酮的外消旋作用的第一个详细描述。在150℃的路易斯酸存在下，以定量收率开发了不希望的（R）-氯胺酮对映异构体的外消旋化过程，该对映体是由制备NMDA受体拮抗剂（S）-氯胺酮的制备物中产生的。各种常用的Lewis的存在，观察到不同程度的外消旋化的单独的酸，和催化效率均安排如下：的MgCl ₂ ≈的AlCl ₃ >的FeCl ₃ >的ZnCl ₂ > BF ₃ >的CaCl ₂。随后使用1 -（+）-酒石酸拆分消旋的氯胺酮，以41％的收率和99.5％的ee获得（S）-氯胺酮。这种简洁且成本有效的外消旋方法在工业上可用于将废物（R）-氯胺酮对映体再循环到拆分过程中以获得（S）-氯胺酮。

更新日期：2020-01-15

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