From p-Xylene to Ibuprofen in Flow: Three-Step Synthesis by a Unified Sequence of Chemoselective C-H Metalations
SCIE
SCOPUS
- Title
- From p-Xylene to Ibuprofen in Flow: Three-Step Synthesis by a Unified Sequence of Chemoselective C-H Metalations
- Authors
- Lee, H.-J.; Kim, H.; Kim, D.-P.
- Date Issued
- 2019-09
- Publisher
- WILEY-V C H VERLAG GMBH
- Abstract
- Ibuprofen was prepared from an inactive and inexpensive p-xylene by three-step flow functionalizations through chemoselective metalations of benzyl positions in sequence using an in situ generated LICKOR-type superbase. The flow approach in the microreactor facilitated the comprehensive exploration of over 100 conditions in the first-step reaction by varying concentrations, temperatures, solvents, and equivalents of reagents, enabling optimal conditions to be found with 95 % yield by significantly suppressing the formation of byproducts, followed by the second C-H metalation step in 95 % yield. Moreover, gram-scale synthesis of ibuprofen in the final step was achieved by biphasic flow reaction of solution-phase intermediate with CO2, isolating 2.3 g for 10 min of operation time.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/107944
- DOI
- 10.1002/chem.201903267
- ISSN
- 0947-6539
- Article Type
- Article
- Citation
- CHEMISTRY-A EUROPEAN JOURNAL, vol. 25, no. 50, page. 11641 - 11645, 2019-09
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.