Hydrogenation of imine intermediates of sertraline with catalysts

Abstract

Provided are hydrogenation processes of sertraline imine intermediates with catalysts in various reactors.

1 - 22 . (canceled)  
     
     
         23 . A process for preparing sertraline from an imine having the formula:  
       
         
           
           
               
               
           
         
         wherein Y is optionally an oxygen atom, comprising the step of hydrogenating the imine with a metal catalyst in a trickel bed reactor and converting the hydrogenated compound to sertraline if necessary.  
       
     
     
         24 . The process of  claim 23 , wherein the metal is nickel.  
     
     
         25 . The process of  claim 24 , wherein Y is not substituted.  
     
     
         26 . The process of  claim 24 , wherein the catalyst has an oxidation state of zero.  
     
     
         27 . The process of  claim 24 , wherein the catalyst has a nickel content of about 30 to about 80% wt/wt.  
     
     
         28 . The process of  claim 24 , wherein the catalyst has a surface area of about 50 to about 200 m 2 /g.  
     
     
         29 . The process of  claim 24 , wherein the nickel is fixed to an alumina-silica support.  
     
     
         30 . The process of  claim 24 , wherein the hydrogenating is carried out at a temperature of about 65 to about 150° C.  
     
     
         31 . The process of  claim 30 , wherein the temperature is about 90° C.  
     
     
         32 . The process of  claim 24 , wherein the hydrogenating is carried out at a pressure of about 2 to about 15 bar.  
     
     
         33 . The process of  claim 32 , wherein the pressure is of about 8 to about 10 bar.  
     
     
         34 . The process of  claim 24 , wherein the imine is fed as a solution in THF having a concentration of about 10 to about 140 grams/L.  
     
     
         35 . The process of  claim 24 , wherein the hydrogenating is carried out with a weight hourly space velocity of about 40 to about 120 per hour.  
     
     
         36 . The process of  claim 24 , wherein hydrogenating is carried out with a hydrogen feed rate of about GHSV 50 to about 2000 per hour.  
     
     
         37 . The process of  claim 24 , wherein the catalyst has granules selected from the group consisting of about 30 to about 50 mesh and about 50 to about 80 mesh.  
     
     
         38 . The process of  claim 24 , wherein the sertraline has a cis to trans ratio of about 7 to 1.  
     
     
         39 . The process of  claim 24 , wherein the hydrogenating results in dechlorinated side products of about 0.1%.  
     
     
         40 . The process of  claim 24 , further comprising increasing ratio of (+)-cis-sertraline through selective precipitation with mandeleic acid.  
     
     
         41 . The process of  claim 24 , further comprising the step of converting the sertraline to sertraline hydrochloride.  
     
     
         42 - 62 . (canceled)  
     
     
         63 . A process for preparing sertraline from sertraline-1-imine comprising the step of hydrogenating sertraline-1-imine in the presence of a catalyst in a trickel bed reactor.  
     
     
         64 . The process of  claim 63 , wherein a cobalt catalyst is used for hydrogenation.  
     
     
         65 - 75 . (canceled)  
     
     
         76 . Sertraline or a hydrochloride salt thereof in solid state comprising less than about 0.1% of the dechlorinated side products as area percentage HPLC according to U.S. Pharmacopoeia.  
     
     
         77 . The sertraline of  claim 76 , wherein the dechlorinated compounds are about 0.05%.  
     
     
         78 . A pharmaceutical composition comprising of sertraline hydrochloride of  claim 76 , and a pharmaceutically acceptable excipient.  
     
     
         79 . A process for preparing a cobalt catalyst suitable for reduction of sertraline-1-imine comprising the steps of: 
 a) calcining an alumina-silica support;    b) evaporating moisture from the calcined support;    c) contacting the calcined support with an aqueous solution of cobalt nitrate to saturate the surface of the support to obtain a catalyst;    d) drying the catalyst; and    e) calcining the catalyst in the presence of hydrogen to obtain an oxidation state of CoO.    
     
     
         80 . The process of  claim 79 , wherein the calcining is carried out by heating to a temperature of at least about 450° C.  
     
     
         81 . The process of  claim 80 , wherein the temperature is about 500° C.  
     
     
         82 . The process of  claim 79 , wherein evaporating is carried out under reduced pressure.  
     
     
         83 . The process of  claim 79 , wherein the drying is carried out of about 100° C. to about 140° C.  
     
     
         84 . The process of  claim 83 , wherein the temperature is about 120° C.  
     
     
         85 . The process of  claim 79 , wherein the hydrogen is added to a reactor at a rate of about GHSV 2000 h −1  to about 3000 h −1 .  
     
     
         86 . The process of  claim 85 , wherein the hydrogen is added at a rate of about GHSV 2500 per hour.  
     
     
         87 . The catalyst prepared by the process of  claim 79.