Processes and intermediates for the preparations of carboprost and carboprost tromethamine, and carboprost tromethamine prepared therefrom

Abstract

The invention relates to processes for preparing Carboprost or Carboprost Tromethamine, and intermediates prepared from the process, and 5,6-trans isomer free Carboprost or Carboprost Tromethamine prepared therefrom. The invention also relates to a novel crystalline form of Carboprost Tromethamine.

1 - 11 . (canceled) 
     
     
         12 . A crystalline for of Carboprost Tromethamine, having a differential scanning calorimetry (DSC) thermogram pattern comprising an endothermic peak with a peak maximum of 106.4±1.0° C., and having an X-ray powder diffraction (XRPD) pattern comprising characteristic peaks at the following 2θ reflection angles: 6.9±0.2°, 10.3±0.2°, 18.8±0.2°, and 21.9±0.2°. 
     
     
         13 . The crystalline form of Carboprost Tromethamine according to  claim 12 , wherein the XRPD pattern further comprises characteristic peaks at the following 2θ reflection angles: 9.1±0.2°, 9.5±0.2°, 11.0±0.2°, and 20.5±0.2°. 
     
     
         14 . The crystalline form of Carboprost Tromethamine according to  claim 12 , containing less than 0.1% 5,6-trans isomer. 
     
     
         15 . The crystalline form of Carboprost Tromethamine according to  claim 14 , containing less than 0.03% 5,6-trans isomer. 
     
     
         16 . A process for preparing the crystalline form of Carboprost Tromethamine according to  claim 12 , comprising the steps of:
 (a) adding Carboprost Tromethamine into anhydrous acetonitrile to form a mixture, wherein the anhydrous acetonitrile is in an amount of from 80 to 250 ml per 1 g of Carboprost Tromethamine;   (b) heating the mixture to a temperature ranging from 70° C. to 90° C. to give a homogeneous solution; and   (c) cooling down the homogeneous solution to form the crystalline form of Carboprost Tromethamine.   
     
     
         17 . The process according to  claim 16 , wherein the anhydrous actonitrile has a water content of less than 0.05%.