A multistep continuous manufacturing process to synthesize (1R,2R)-2-amino-1-methylcyclopentan-1-ol (2) was developed. The step 1/2 flow process mitigated the safety hazard associated with high exothermicity during epoxidation, the epoxide-opening reaction, and the low onset of the epoxide intermediate. Process improvements included a hybrid plug flow reactor (PFR)/continuous stirred tank reactor (CSTR) reaction and a continuous quench/work-up process in step 1; a continuous reaction, extraction, washing, and thin-film distillation work-up in step 2; and a continuous trickle bed hydrogenation in step 3, which provided the desired product with high purity and high ee. The end-to-end continuous process provided significant advantages of cost-saving, minimization of manufacturing space and utilities, and reduction of the cycle time.

中文翻译：

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开发（1 R，2 R）-2-氨基-1-甲基环戊烷-1-醇的多步连续制造工艺

合成（1 R，2 R）-2-氨基-1-甲基环戊烷-1-醇（2） 已开发。步骤1/2的流动过程减轻了与环氧化过程中的高放热，环氧化物的开放反应以及环氧化物中间体的低起始有关的安全隐患。工艺改进包括步骤1中的混合活塞流反应器（PFR）/连续搅拌釜反应器（CSTR）反应和连续淬火/后处理工艺。步骤2中的连续反应，萃取，洗涤和薄膜蒸馏后处理；在步骤3中进行连续滴流床加氢，可提供所需的产物，具有高纯度和高ee。端到端连续过程提供了节省成本，最大程度地减少制造空间和实用性以及缩短周期时间的显着优势。