Purification of Dirithromycin. Impurity Reduction and Polymorph Manipulation

详细信息    查看全文

• 作者：David D. Wirth and and Gregory A. Stephenson
• 刊名：Organic Process Research & Development
• 出版年：1997
• 出版时间：January 1997
• 年：1997
• 卷：1
• 期：1
• 页码：55 - 60
• 全文大小：296K
• 年卷期：v.1,no.1(January 1997)
• ISSN：1520-586X

文摘

The manufacture of dirithromycin[9S(R)-9-deoxo-11-deoxy-9,11-[imino[2-(2-methoxyethoxy)ethylidene]oxy]erythromycin] from commercially available erythromycin Aresults in a drug substance containing impurities at thelevelof several percent. A five-step plan for the development ofacommercial-scale recrystallization procedure is presented.Apurification system for dirithromycin which utilizes thecrystalline acetone solvate and exemplifies this plan isdescribed.Physical characterization data for this solvate are included.Thesolubility of the acetone solvate in water-acetone mixturesisat a maximum at a ratio of 1:9 v/v and exhibits aparabolicrelationship with temperature such that, in a solventcomposition of 2:1, its solubility is at a minimum at 40 C. Theadductof erythromycylamine and acetone was found to exist insolutionas an equilibrium between the tetrahydro-1,3-oxazine andimineforms.