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Development and Execution of a Production-Scale Continuous [2 + 2] Photocycloaddition

  • Matthew G. Beaver*
    Matthew G. Beaver
    Process Development, Amgen, Inc., 360 Binney Street, Cambridge, Massachusetts 02142, United States
    *Email: [email protected]
  • En-xuan Zhang*
    En-xuan Zhang
    Asymchem Life Science (Tianjin) Co., Ltd., No. 71 Seventh Avenue, TEDA, Tianjin 300457, China
    *Email: [email protected]
  • Zhi-qing Liu
    Zhi-qing Liu
    Asymchem Life Science (Tianjin) Co., Ltd., No. 71 Seventh Avenue, TEDA, Tianjin 300457, China
    More by Zhi-qing Liu
  • Song-yuan Zheng
    Song-yuan Zheng
    Asymchem Life Science (Tianjin) Co., Ltd., No. 71 Seventh Avenue, TEDA, Tianjin 300457, China
  • Bin Wang
    Bin Wang
    Asymchem Life Science (Tianjin) Co., Ltd., No. 71 Seventh Avenue, TEDA, Tianjin 300457, China
    More by Bin Wang
  • Jiang-ping Lu
    Jiang-ping Lu
    Asymchem Life Science (Tianjin) Co., Ltd., No. 71 Seventh Avenue, TEDA, Tianjin 300457, China
  • Jian Tao
    Jian Tao
    Asymchem Life Science (Tianjin) Co., Ltd., No. 71 Seventh Avenue, TEDA, Tianjin 300457, China
    More by Jian Tao
  • Miguel Gonzalez
    Miguel Gonzalez
    Asymchem Life Science (Tianjin) Co., Ltd., No. 71 Seventh Avenue, TEDA, Tianjin 300457, China
  • Siân Jones
    Siân Jones
    Process Development, Amgen, Inc., Thousand Oaks, California 91320, United States
    More by Siân Jones
  • , and 
  • Jason S. Tedrow
    Jason S. Tedrow
    Process Development, Amgen, Inc., 360 Binney Street, Cambridge, Massachusetts 02142, United States
Cite this: Org. Process Res. Dev. 2020, 24, 10, 2139–2146
Publication Date (Web):May 27, 2020
https://doi.org/10.1021/acs.oprd.0c00185
Copyright © 2020 American Chemical Society

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    Abstract

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    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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