Optical Resolution of a 1,5-Benzothiazepine Derivative, a Synthetic Intermediate of Diltiazem, by Preferential Crystallization and Diastereomeric Salt Formation
| Autor: | Takeji Shibatani, Shinichi Yamada, Ryuzo Yoshioko |
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| Rok vydání: | 1997 |
| Předmět: |
Aqueous solution
Tertiary amine Bicyclic molecule Thiazepines Stereochemistry Temperature Diastereomer Stereoisomerism General Chemistry General Medicine Medicinal chemistry law.invention Diltiazem chemistry.chemical_compound chemistry law Yield (chemistry) Drug Discovery Lactam Fractional crystallization (chemistry) Crystallization |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 45:1922-1927 |
| ISSN: | 1347-5223 0009-2363 |
| DOI: | 10.1248/cpb.45.1922 |
| Popis: | Practical preparation methods of an optically active intermediate of diltiazem, (+)-(2S, 3S)-5-[2-(dimethylamino)ethyl]-2, 3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1, 5-benzothiazepin-4(5H)-one [(+)-7], have been developed by the use of physicochemical and chemical resolutions. 1) The salt of (±)-7 with 3-amino-4-hydroxy-benzenesulfonic acid (AHS), was found to exist as a conglomerate and could be reproducibly resolved into (+)-7·AHS and (-)-7·AHS of 94-98% ee by a preferential crystallization procedure. 2) (+)-(1R)-3-Bromocamphor-9-sulfonic acid [(+)-BCS] was found to be an efficient resolving agent for (±)-7 and the diasteoremeric resolution provided (+)-7·(+)-BCS·2H2O salt in >43% yield and >97% ee by fractional crystallization. It is presumed that the crystal water of (+)-7·(+)-BCS·2H2O plays an important role in the selective crystallization during this efficient resolution. |
| Databáze: | OpenAIRE |
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