A Facile Synthesis of Substituted 5-11-Dihydro[1]benzoxepinol[3,4-b]pyridines

Kunimi Inoue; Toru Sugaya; Takehiro Ogasa; Shinji Tomioka

doi:10.1055/s-1997-1503

Synthesis 1997; 1997(1): 113-116
DOI: 10.1055/s-1997-1503

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A Facile Synthesis of Substituted 5-11-Dihydro[1]benzoxepinol[3,4-b]pyridines

Kunimi Inoue¹ , Toru Sugaya² , Takehiro Ogasa² , Shinji Tomioka³

¹Sakai Research Laboratories, Kyowa Hakko Kogyo Co., Ltd. 1-1-53 Takasu-cho, Sakai, Osaka 590, Japan, Fax +81(722)277214
²Sakai Research Laboratories, Kyowa Hakko Kogyo Co., Ltd. 1-1-53 Takasu-cho, Sakai, Osaka 590, Japan
³Yokkaichi Research Laboratories, Kyowa Hakko Kogyo Co., Ltd. 2-3 Daikyo-cho, Yokkaichi, Mie 510, Japan, Fax +81(593)333374

Abstract

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5-Amino-5,11-dihydro[1]benzoxepino[3,4-b]pyridines (1) show antiulcer and antiarrhythmic activity. An efficient method for the preparation of a key intermediate, furo[3,4-b]pyridin-5(7 H)-one (4), and the facile synthesis of 1 were described. The reduction of quinolinic anhydride (5) with sodium borohydride in the presence of acetic acid regioselectively gave the lactone 4. Lactone 4 was then reacted with substituted phenols under basic conditions and the resultant products, 2-(phenoxymethyl)-3-pyridinecarboxylic acids (3), underwent Friedel-Crafts cyclizations to produce the 5,11-dihydro[1]benzoxepino[3,4-b]pyridin-5-ones (2). Compounds 2 were then converted to imines with amines and successively reduced with zinc in acetic acid to the desired compounds 1.

quinolinic anhydride - regioselective reduction - azaphthalide Friedel-Crafts cyclization - 5,11-dihydro[1]benzoxepino-[3,4-b]pyridine

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