The process of resolution of racemic ketoprofen using n-octyl-d-glucamine as an optical resolution agent was investigated. The process consists of preparation of the diastereomer salt of ketoprofen with n-octyl-d-gluc...The process of resolution of racemic ketoprofen using n-octyl-d-glucamine as an optical resolution agent was investigated. The process consists of preparation of the diastereomer salt of ketoprofen with n-octyl-d-glucamine, liberation of S-(+)-ketoprofen from its diastereomer salt and recovery of the remaining ketoprofen and n-octyl-d- glucamine. The suitable conditions for preparation of the diastereomer salt were methanol and ethyl acetate (1.1 by volume) as the solvent, the ratio of solvent volume to ketoprofen mass at 8ml:1g, and the molar ratio of ketoprofen to n-octyl-d-glucamine at 1:1. The preferred approach to liberate S-(+)-ketoprofen from its diastereomer salt was alkali dissolution, acid adjustment and ethyl acetate extraction. Racemization of the recovered ketoprofen could be achieved by reacting the recovered ketoprofen with 10% NaOH at 507 kPa for 6h. The recovered n-octyl-d- glucamine could be refined by acid dissolution and alkali adjustment. S-(+)-ketoprofen can be obtained with high optical purity and yield, showing that the present process is a practical and efficient one which can be used in industrial scale for preparation of S-(+)-ketoprofen.展开更多
文摘The process of resolution of racemic ketoprofen using n-octyl-d-glucamine as an optical resolution agent was investigated. The process consists of preparation of the diastereomer salt of ketoprofen with n-octyl-d-glucamine, liberation of S-(+)-ketoprofen from its diastereomer salt and recovery of the remaining ketoprofen and n-octyl-d- glucamine. The suitable conditions for preparation of the diastereomer salt were methanol and ethyl acetate (1.1 by volume) as the solvent, the ratio of solvent volume to ketoprofen mass at 8ml:1g, and the molar ratio of ketoprofen to n-octyl-d-glucamine at 1:1. The preferred approach to liberate S-(+)-ketoprofen from its diastereomer salt was alkali dissolution, acid adjustment and ethyl acetate extraction. Racemization of the recovered ketoprofen could be achieved by reacting the recovered ketoprofen with 10% NaOH at 507 kPa for 6h. The recovered n-octyl-d- glucamine could be refined by acid dissolution and alkali adjustment. S-(+)-ketoprofen can be obtained with high optical purity and yield, showing that the present process is a practical and efficient one which can be used in industrial scale for preparation of S-(+)-ketoprofen.
