Journal article
Scalable synthesis of (R,R)-N,N-dibenzyl-2-fluorocyclohexan-1-amine with CsF under hydrogen bonding phase-transfer catalysis
- Abstract:
- Hydrogen bonding phase-transfer catalysis offers a convenient solution to activate safe and economical metal alkali fluorides for enantioselective nucleophilic fluorination. Herein, we demonstrate the scalability of this protocol with the fluorination of 200 g of racemic trans-N,N-dibenzyl-2-bromocyclohexan-1-amine in a mechanically stirred 1 L glass reactor using 0.5 mol % of a bis-urea organocatalyst. In these experiments, full conversions were obtained for high mixing intensities (impeller average shear rate >10 000 s–1; maximum energy dissipation per unit of mass >300 W/kg). The thermal safety of the reaction was assessed by differential scanning calorimetry and reaction calorimetry, assigning the reaction to Stoessel’s critical class 3.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
-
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(Preview, Accepted manuscript, pdf, 751.1KB, Terms of use)
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(Preview, Supplementary materials, pdf, 1.9MB, Terms of use)
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- Publisher copy:
- 10.1021/acs.oprd.1c00312
Authors
- Publisher:
- American Chemical Society
- Journal:
- Organic Process Research and Development More from this journal
- Volume:
- 25
- Issue:
- 13
- Pages:
- 2730-2737
- Publication date:
- 2021-12-03
- Acceptance date:
- 2021-12-03
- DOI:
- EISSN:
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1520-586X
- ISSN:
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1083-6160
- Language:
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English
- Keywords:
- Pubs id:
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1217189
- Local pid:
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pubs:1217189
- Deposit date:
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2021-12-03
- ARK identifier:
Terms of use
- Copyright holder:
- American Chemical Society
- Copyright date:
- 2021
- Rights statement:
- © 2021 American Chemical Society.
- Notes:
-
This is the accepted manuscript version of the article. The final version is available from American Chemical Society at https://doi.org/10.1021/acs.oprd.1c00312
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