Optical resolution and absolute configuration of a nonsteroidal antiinflammatory drug, 2-(10,11-Dihydro-10-oxodibenzo-[b,f]thiepin-2-yl)propionic acid

✍ Scribed by Masao Yamamoto; Hiroyuki Nohira; Mitsuo Masaki

• Book ID: 102075649
• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 342 KB
• Volume: 2
• Category: Article
• ISSN: 0899-0042
• DOI: 10.1002/chir.530020415

✦ Synopsis

Abstract

The title compound (±)‐1 (CN‐100) was efficiently resolved into a pair of enantiomers by fractional crystallization of the diastereomeric salts of (−)‐and (+)‐1‐phenylethylamine. The purity of the enantiomers was determined using the chiral cellulose column (CHIRALCEL OJ^®^) which allowed direct separation of the enantiomers. A separation factor (α) of 1.73 was obtained. X‐Ray crystallographic analysis of the (+)‐isomer [salt of (−)‐1‐(4‐bromophenyl)ethylamine] showed that this enantiomer has S‐configuration. Biological studies have shown that only the (+)‐isomer has antiinflammatory activity. Racemization of (−)‐isomer was carried out by heating its propionic acid solution in the presence of mineral acid, such as HBr.