Optimized Process and Quality Evaluation for Ketamine Hydrochloride

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED Organic Process Research & Development Pub Date : 2023-06-26 DOI:10.1021/acs.oprd.3c00082

Bibo Jiang, Haibo Pan, Jiajia Liu, Xiaojie Zhang, Qian Wang, Tao Zhang* and Fuli Zhang*,

引用次数: 0

Abstract

In this study, we developed an enhanced and efficient kilogram-scale synthesis method for ketamine hydrochloride. We discovered that using N-bromosuccinimide (NBS) instead of HBr/H₂O₂ improved the conversion rate of the bromination reaction from 88% to 99% and led to a milder and steadier reaction. Besides, CH₃NH₂/K₂CO₃ was used in the methylamination reaction to shorten the reaction time from 80 to 15 h, with an 80% yield of 1-((2-chlorophenyl) (methylimino) methyl) cyclopentanol hydrochloride (6) and 99.5% purity. Furthermore, the residue on ignition of ketamine hydrochloride decreased from 3.00% to below 0.10% with extra aqueous base washing. Several related impurities of ketamine hydrochloride were also assessed, and the clarity and color of the ketamine hydrochloride solution were investigated. In summary, the optimized process was industrially scalable and able to control the final quality of ketamine hydrochloride.

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盐酸氯胺酮的工艺优化及质量评价

在本研究中，我们开发了一种改进的、高效的公斤级合成盐酸氯胺酮的方法。研究发现，用n -溴代琥珀酰亚胺(NBS)代替HBr/H2O2可将溴化反应的转化率从88%提高到99%，反应更温和、更稳定。采用CH3NH2/K2CO3进行甲基层化反应，将反应时间从80 h缩短至15 h, 1-(2-氯苯基)(甲基基)甲基)环戊醇盐酸盐(6)的收率为80%，纯度为99.5%。加水碱洗后，盐酸氯胺酮的着火残渣由3.00%降至0.10%以下。对盐酸氯胺酮的相关杂质进行了评价，并对盐酸氯胺酮溶液的纯度和颜色进行了考察。综上所述，优化后的工艺具有工业可扩展性，能够控制盐酸氯胺酮的最终质量。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

期刊介绍： The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.

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