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Practical synthesis of PGI agonist: Resolution-inversion- recycle approach of its chiral intermediate

Organic Process Research and Development, ISSN: 1083-6160, Vol: 17, Issue: 4, Page: 658-665
2013
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Article Description

Practical synthesis of ((2R)-5-benzyloxy-2-hydroxy-1,2,3,4- tetrahydronaphth-2-yl)methanol ((R)-7b), a key chiral intermediate for the synthesis of the novel PGI agonist, (R)-[6-[(diphenylcarbamoyloxy) methyl]-6-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yloxy]acetic acid (1), was achieved via optical resolution by diastereoselective crystallization of ester derivative 18 of racemic (5-benzyloxy-2-hydroxy-1,2,3,4-tetrahydronaphth-2-yl) methanol (7b) with (1S,4R)-(-)-camphanic acid ((-)-CpOH) followed by saponification. Starting from commercially available 5-hydroxy-1-tetralone (2), this process features recycling of the undesired enantiomer (S)-7b via inversion of the C2 hydroxyl group by acid-catalyzed hydrolysis of its epoxide derivative (S)-11. Performing this resolution-inversion-recycle approach provided a 44% overall yield of (R)-7b (>99% ee) from racemic 7b. The enantiopure (R)-7b synthesized by this approach was then used to prepare 1. This robust, reproducible, and scalable synthesis of 1 was successfully demonstrated on a pilot scale. © 2013 American Chemical Society.

Bibliographic Details

Atsushi Ohigashi; Atsushi Kanda; Shigeru Moriki; Yukihisa Baba; Norio Hashimoto; Minoru Okada

American Chemical Society (ACS)

Chemistry

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