Development and Execution of a Production-Scale Continuous [2 + 2] Photocycloaddition
- Matthew G. Beaver*Matthew G. Beaver*Email: [email protected]Process Development, Amgen, Inc., 360 Binney Street, Cambridge, Massachusetts 02142, United StatesMore by Matthew G. Beaver
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- En-xuan Zhang*En-xuan Zhang*Email: [email protected]Asymchem Life Science (Tianjin) Co., Ltd., No. 71 Seventh Avenue, TEDA, Tianjin 300457, ChinaMore by En-xuan Zhang
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- Zhi-qing LiuZhi-qing LiuAsymchem Life Science (Tianjin) Co., Ltd., No. 71 Seventh Avenue, TEDA, Tianjin 300457, ChinaMore by Zhi-qing Liu
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- Song-yuan ZhengSong-yuan ZhengAsymchem Life Science (Tianjin) Co., Ltd., No. 71 Seventh Avenue, TEDA, Tianjin 300457, ChinaMore by Song-yuan Zheng
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- Bin WangBin WangAsymchem Life Science (Tianjin) Co., Ltd., No. 71 Seventh Avenue, TEDA, Tianjin 300457, ChinaMore by Bin Wang
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- Jiang-ping LuJiang-ping LuAsymchem Life Science (Tianjin) Co., Ltd., No. 71 Seventh Avenue, TEDA, Tianjin 300457, ChinaMore by Jiang-ping Lu
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- Jian TaoJian TaoAsymchem Life Science (Tianjin) Co., Ltd., No. 71 Seventh Avenue, TEDA, Tianjin 300457, ChinaMore by Jian Tao
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- Miguel GonzalezMiguel GonzalezAsymchem Life Science (Tianjin) Co., Ltd., No. 71 Seventh Avenue, TEDA, Tianjin 300457, ChinaMore by Miguel Gonzalez
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- Siân JonesSiân JonesProcess Development, Amgen, Inc., Thousand Oaks, California 91320, United StatesMore by Siân Jones
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- Jason S. TedrowJason S. TedrowProcess Development, Amgen, Inc., 360 Binney Street, Cambridge, Massachusetts 02142, United StatesMore by Jason S. Tedrow
Abstract

This article details the approach to large-scale production of cyclobutane 2 by the continuous-flow [2 + 2] photocycloaddition of maleic anhydride and ethylene, including (1) focused reaction optimization and development of a robust isolation protocol, (2) the approach to equipment design and process safety, and (3) the results of commissioning tests and production runs delivering the target compound at throughputs exceeding 5 kg/day.
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