Process for preparing tamsulosin

Abstract

The present invention relates to a process for preparing Tamsulosin, an anti-benign prostatic hyperplasia drug, which comprises converting o-ethoxyphenoxyethanol to a corresponding sulfonate, and reacting the sulfonate with (R)-(−)-5-(2-aminopropyl)-2-methoxybenzenesulfonamide by condensation to produce Tamsulosin.

1 . A process for preparing Tamsulosin, which comprises the following step: 
 reacting o-ethoxyphenoxyethanol sulfonate of Formula (3) with R-(−)-5-(2-aminopropyl)-2-methoxybenzenesulfonamide of Formula (4) at a temperature of about 40 to 100° C. by condensation to produce Tamsulosin:                          wherein R is (C 1 -C 6 )alkyl or phenyl substituted by halogen, nitro and/or (C 1 -C 6 )alkyl.    
   
   
       2 . The process according to  claim 1 , wherein said reaction is conducted at a temperature of about 50 to 80° C.  
   
   
       3 . The process according to  claim 2 , wherein said reaction is conducted at a temperature of about 55 to 65° C.  
   
   
       4 . The process according to  claim 1 , wherein said reaction is conducted in the presence of a solvent.  
   
   
       5 . The process according to  claim 4 , wherein said solvent is an aprotic organic solvent.  
   
   
       6 . The process according to  claim 4 , wherein said solvent is selected from the group consisting of N,N-dimethylformamide (DMF), dimethyl sulphoxide (DMSO), N,N-dimethylacetamide (DMAC) and mixtures thereof.  
   
   
       7 . The process according to  claim 1 , wherein an acid scavenger is used in the reaction.  
   
   
       8 . The process according to  claim 7 , wherein said acid scavenger is an organic amine, an inorganic base or combinations thereof.  
   
   
       9 . The process according to  claim 8 , wherein said organic amine is selected from the group consisting of an organic tertiary amine, pyridine and mixtures thereof.  
   
   
       10 . The process according to  claim 9 , wherein said organic amine is selected from the group consisting of triethylamine, pyridine and mixtures thereof.  
   
   
       11 . The process according to  claim 8 , wherein said inorganic base is selected from the group consisting of KOH, NaOH, K 2 CO 3 , NaHCO 3  and mixtures thereof.  
   
   
       12 . The process according to  claim 1 , wherein said reaction is conducted in the presence of a catalyst.  
   
   
       13 . The process according to  claim 12 , wherein said catalyst is a monovalent inorganic iodide.  
   
   
       14 . The process according to  claim 12 , wherein said catalyst is selected from the group consisting of potassium iodide (KI), sodium iodide (NaI), copper iodide (CuI) and mixtures thereof.  
   
   
       15 . A process for preparing o-ethoxyphenoxyethanol sulfonate, which comprises the following step: 
 reacting o-ethoxyphenoxyethanol of Formula (2) with sulfonyl chloride of Formula RSO 2 Cl at a temperature of about −10 to 10° C., to produce o-ethoxyphenoxyethanol sulfonate of Formula (3),                          wherein R is (C 1 -C 6 )alkyl or phenyl substituted by halogen, nitro and/or (C 1 -C 6 )alkyl.    
   
   
       16 . The process according to  claim 15 , wherein said reaction is conducted at a temperature of about −5 to 5° C.  
   
   
       17 . The process according to  claim 16 , wherein said reaction is conducted at a temperature of about 0 to 5° C.  
   
   
       18 . The process according to  claim 15 , wherein said reaction is conducted in the presence of a solvent.  
   
   
       19 . The process according to  claim 18 , wherein said solvent is selected from the group consisting of chloromethane, chloroethane, benzene, substituted benzene, pyridine and mixtures thereof.  
   
   
       20 . The process according to  claim 19 , wherein said solvent is selected from the group consisting of dichloromethane, trichloromethane, dichloroethane, benzene, toluene and mixtures thereof.  
   
   
       21 . A process for preparing Tamsulosin, which sequentially comprises the following steps: 
 (i) reacting o-ethoxyphenoxyethanol of Formula (2) with sulfonyl chloride of Formula RSO 2 Cl at a temperature of about −10 to 10° C., to form o-ethoxyphenoxyethanol sulfonate of Formula (3);                          and    (ii) reacting o-ethoxyphenoxyethanol sulfonate of Formula (3) with R-(−)-5-(2-aminopropyl)-2-methoxybenzenesulfonamide of Formula (4) at a temperature of about 40 to 100° C. by condensation to produce Tamsulosin;                          wherein R is (C 1 -C 6 )alkyl or phenyl substituted by halogen, nitro and/or (C 1 -C 6 )alkyl.    
   
   
       22 . The process according to  claim 21 , wherein said step (i) is conducted at a temperature of about −5 to 5° C.  
   
   
       23 . The process according to  claim 22 , wherein said step (i) is conducted at a temperature of about 0 to 5° C.  
   
   
       24 . The process according to  claim 21 , wherein the step (i) is conducted in the presence of a solvent.  
   
   
       25 . The process according to  claim 24 , wherein said solvent is selected from the group consisting of chloromethane, chloroethane, benzene, substituted benzene, pyridine and mixtures thereof.  
   
   
       26 . The process according to  claim 25 , wherein said solvent is selected from the group consisting of dichloromethane, trichloromethane, dichloroethane, benzene, toluene and mixtures thereof.  
   
   
       27 . The process according to  claim 21 , wherein said step (ii) is conducted at a temperature of about 50 to 80° C.  
   
   
       28 . The process according to  claim 27 , wherein said step (ii) is conducted at a temperature of about 55 to 65° C.  
   
   
       29 . The process according to  claim 21 , wherein said step (ii) is conducted in the presence of a solvent.  
   
   
       30 . The process according to  claim 29 , wherein said solvent is an aprotic organic solvent.  
   
   
       31 . The process according to  claim 29 , wherein said solvent is selected from the group consisting of N,N-dimethylformamide (DMF), dimethyl sulphoxide (DMSO), N,N-dimethylacetamide (DMAC) and mixtures thereof.  
   
   
       32 . The process according to  claim 21 , wherein an acid scavenger is used in step (ii).  
   
   
       33 . The process according to  claim 32 , wherein said acid scavenger is an organic amine, an inorganic base or combinations thereof.  
   
   
       34 . The process according to  claim 33 , wherein said organic amine is selected from the group consisting of an organic tertiary amine, pyridine and mixtures thereof.  
   
   
       35 . The process according to  claim 34 , wherein said organic amine is selected from the group consisting of triethylamine, pyridine and mixtures thereof.  
   
   
       36 . The process according to  claim 33 , wherein said inorganic base is selected from the group consisting of KOH, NaOH, K 2 CO 3 , NaHCO 3  and mixtures thereof.  
   
   
       37 . The process according to  claim 21 , wherein said step (ii) is conducted in the presence of a catalyst.  
   
   
       38 . The process according to  claim 37 , wherein said catalyst is a monovalent inorganic iodide.  
   
   
       39 . The process according to  claim 37 , wherein said catalyst is selected from the group consisting of: potassium iodide (KI), sodium iodide (NaI), copper iodide (CuI) and mixtures thereof.