Resolution of substituted dibenzo b,f!thiepin-3-carboxylic acid-5- oxides with brucine or ephedrine

摘要

The present invention is concerned with an improved process for the production of highly active optical isomers of (-) 7 or 8 fluorodibenzo b, f!thiepin-3-carboxylic acid-5-oxide having the structural formula ##STR1## in which the fluoro substituent replaces a hydrogen in the 7 or 8 position. The two active isomers represented by formula II are S(-)7- fluorodibenzo b,f!thiepin-3-carboxylic acid-5-oxide and R(-)8- fluorodibenzo b,f!thiepin-3-carboxylic acid-5-oxide. It is especially concerned with the resolution of the racemic 7 or 8 fluorodibenzo b, f!thiepin-3-carboxylic acid-5-oxide by first forming and separating diastereomers of said racemic carboxylic acids by salt formation with brucine or ephedrine followed by crystallization and regeneration of the desired (-) isomers and recycling of the (+) isomer by racemization of the regenerated isomer. The compounds obtained in high yield by this process are highly active prostaglandin antagonists which are useful in treating a variety of conditions such as allergic asthma.