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COMMUNICATION
Chemical Communication
obtain 5 as summarized in (Table S5). The reaction performance
generally depended on the residence time of 3 at fixed flow rate of
base triethylamine (TEA). In the range of molar ratio of 2.25 (TEA/3),
the optimized reaction resulted in 99% conversion (Table S5, entry 3)
Ehara, M.; Karanjit, S.; Sakurai, H. J. Am. Chem. Soc. 2012, 134, 20250.
DOI: 10.1039/C9CC06127D
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within 2ꢀmin of residence time at 80 C temperature and 5 bar
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pressure, resulting in ∼36ꢀmmolꢀh productivity of 5. We next
focused our attention on the cyclization reaction, which involves the
treatment of compound 5 with ammonium acetate to form DCV in
excellent yield (∼84%) (Fig. 5, step 3) in 3.2 min residence time at 160
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o
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12 (a) Li, C.; Kawamata, Y.; Nakamura, H.; Vantourout, J. C.; Liu, Z.; Hou, Q.;
C temperature and 17 bar pressure, resulting in ∼34ꢀmmolꢀh
Bao, D.; Starr, J. T.; Chen, J.; Yan, M.; Baran, P. S. Angew. Chem. Int. Ed.
productivity using the continuous flow platform (Table S6, entry 3).
In contrast, the conventional batch process required a longer
reaction time (3-10 days) to attain overall ∼22-45% yield, while
continuous flow process enhanced the overall yield 77% in 33.2 min
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of residence time. Such a striking contrast highlights the additional
power of the continuous flow system that results when it is
combined with multi-component reaction. Additional, integrated
continuous one-flow multi-step DCV synthesis work is under
progress in our lab.
In conclusion, we have developed an integrated total process system
including development of electro-flow reactor containing patterned
electrodeposited Ni/Pt metal over the copper electrode for C-C coupling
reaction. The examination of the haloarenes to multistep sequences
afforded ultra-fast DCV API synthesis with improved yield. An advanced
(f) Heider, P. L.; Born, S. C.; Basak, S.; Benyahia, B.; Lakerveld, R.; Zhang,
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EFR platformincontinuousflowchemistry, andwithanadditionalplug
and play research, ultimately enables the continuous synthesis of modern
small molecule pharmaceuticals, including enantiopure APIs. More
importantly, the developed system detailed here would enable the future
automation of research laboratory and chemical industry to produce on-
demand ultra-fast structural complex APIs (DCV, velpatasvir, and
ledipasvir) and commodity chemicals synthesis in the areas of drug
discovery, natural products, materials synthesis, and biology.
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(
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A.K.S. thanks Department of Science and Technology, New Delhi (Govt.
of India) (DST), New Delhi, for the INSPIRE Faculty Award and Early Career
Research Award. Financial assistance received from CSIR (HCP-0011), DST
and Science and Engineering Research Board (SERB) project no.
DST/INSPIRE/04/2016/000247 and ECR/2017/000208 are gratefully
acknowledged. We gratefully acknowledge Director, CSIR-IICT for his
support and encouragement. CSIR-IICT, Hyderabad, has filed a patent on
the process reported herein. CSIR-IICT manuscript communication no.
IICT/Pubs./2019/214.
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