Synthèse de l'Oxetorone (14C-6) : (diméthylamino-3 propylidène-1)-6 benzofuro [2,3-e] 12H-benzo [b] oxépine (14C-6). Séparation chromatographique des isomères (E) et (Z)
✍ Scribed by J. P. Noel; L. Pichat; A. Benakis
- Publisher
- John Wiley and Sons
- Year
- 1983
- Tongue
- French
- Weight
- 458 KB
- Volume
- 20
- Category
- Article
- ISSN
- 0022-2135
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✦ Synopsis
Abstract
Synthesis and chromatographic separation of (E) and (Z) isomers of [6‐^14^C] oxetorone : [6‐^14^C] 6‐(3‐Dimethylaminopropylidene)[2, 3‐e] benzofuro‐12H‐benzo [b] oxepin^*^, hydrogen fumarate. A new synthesis of [6‐^14^C] oxetorone was devised allowing the three step preparation from ^14^CO~2~ of this drug used in the treatment of migraine. 2‐bromo‐3‐phenoxymethyl benzo [b] furan : 10 was prepared from 3‐methyl [b] furan 7. In diethyl ether 10 gave with n‐butyllithium the corresponding : 2‐lithio 3‐phenoxymethyl benzo [b] furan the carbonation of which with ^14^CO~2~ gave [2‐carboxy ^14^C] 3‐phenoxymethyl benzo [b] furan in a 70% yield based on ^14^CO~2~. The carboxylic acid 5 was transformed into the corresponding acyl halide which was ring closed into [6‐^14^C] oxepinone 6. Condensation of the latter with 3‐dimethylaminopropyl magnesium chloride followed by dehydration under hydrochloric acid treatment and isolation as fumarate gave [6‐^14^C] oxetorone with an overall yield of 24% based on ^14^CO~2~. The (E) and (Z) isomers of oxetorone were separated by reverse phase HPLC.