Synfacts 2008(3): 0315-0315  
DOI: 10.1055/s-2008-1042669
Polymer-Supported Synthesis
© Georg Thieme Verlag Stuttgart · New York

Traceless Solid-Phase Preparation of Thiomorpholin-3-ones

Contributor(s): Yasuhiro Uozumi. Yoichi M. A. Yamada
K. Saruta*, T. Ogiku
Mitsubishi Tanabe Pharma Corporation, Osaka, Japan
Further Information

Publication History

Publication Date:
21 February 2008 (online)


Preparation of thiomorpholin-3-ones 10 using a traceless solid-phase approach was described. Thus, the reaction of benzyl chloride on Merrifield resin 1 with 2 gave the corresponding products 3 that were converted into N,N-disubstituted 2-nitrobenzenesulfonamides 5 under Mitsunobu conditions with 4. Compounds 5 were transformed into the key intermediates 8 by removal of the Ns group followed by acylation with chloroacetic acids 7. The key cyclization of 8 was carried out with CsI (1 equiv) in aqueous dioxane to afford thiomorpholin-3-ones 10 via cyclic sulfonium salts 9. Six-, seven-, and eight-membered products 10 were obtained in 47-74% yield with 95-100% purity.