Process for producing 6, 7-bis (2-methoxyethoxy)-quinazolin-4-one

Abstract

A process comprising a reaction of ethyl 2-amino-4,5-bis(2-methoxyethoxy)benzoate with a formic acid compound in the presence of an ammonium carboxylate gives 6,7-bis(2-methoxyethoxy)quinazolin-4-one in a high yield.

1 . A process for preparation of 6,7-bis(2-methoxyethoxy)quinazolin-4-one, which comprises causing a reaction of ethyl 2-amino-4,5-bis(2-methoxyethoxy)benzoate with a formic acid compound in the presence of an ammonium carboxylate.  
   
   
       2 . A process for preparation of 6,7-bis(2-methoxyethoxy)quinazolin-4-one, which comprises the steps in order of: causing a reaction of ethyl 4,5-bis(2-methoxyethoxy)-2-nitrobenzoate with hydrogen in the presence of a metallic catalyst to prepare ethyl 2-amino-4,5-bis(2-methoxyethoxy)benzoate; and causing a reaction of the ethyl 2-amino-4,5-bis(2-methoxyethoxy)benzoate with a formic acid compound in the presence of an ammonium carboxylate to prepare 6,7-bis(2-methoxyethoxy)-quinazolin-4-one.  
   
   
       3 . A process for preparation of 6,7-bis(2-methoxyethoxy)quinazolin-4-one, which comprises the steps in order of: causing a reaction of ethyl 3,4-bis(2-methoxyethoxy)benzoate with nitric acid in the presence of sulfuric acid to prepare ethyl 4,5-bis(2-methoxyethoxy)-2-nitrobenzoate; causing a reaction of the ethyl 4,5-bis(2-methoxyethoxy)-2-nitrobenzoate with hydrogen in the presence of a metallic catalyst to prepare ethyl 2-amino-4,5-bis(2-methoxyethoxy)benzoate; and causing a reaction of the ethyl 2-amino-4,5-bis(2-methoxyethoxy)benzoate with a formic acid compound in the presence of an ammonium carboxylate to prepare 6,7-bis(2-methoxyethoxy)-quinazolin-4-one.  
   
   
       4 . A process for preparation of 6,7-bis(2-methoxyethoxy)quinazolin-4-one, which comprises the steps in order of: causing a reaction of ethyl 3,4-dihydroxybenzoate with 2-chloroethyl methyl ether in an organic solvent in the presence of a base to prepare ethyl 3,4-bis(2-methoxyethoxy)benzoate; causing a reaction of the ethyl 3,4-bis(2-methoxyethoxy)benzoate with nitric acid in the presence of sulfuric acid to prepare ethyl 4,5-bis(2-methoxyethoxy)-2-nitrobenzoate; causing a reaction of the ethyl 4,5-bis(2-methoxyethoxy)-2-nitrobenzoate with hydrogen in the presence of a metallic catalyst to prepare ethyl 2-amino-4,5-bis(2-methoxyethoxy)benzoate; and causing a reaction of the ethyl 2-amino-4,5-bis(2-methoxyethoxy)benzoate with a formic acid compound in the presence of an ammonium carboxylate to prepare 6,7-bis(2-methoxyethoxy)quinazolin-4-one.  
   
   
       5 . The process according to one of the  claims 1  to  4 , wherein the formic acid compound is an orthoformic ester.  
   
   
       6 . The process according to one of the  claims 1  to  4 , wherein the ammonium carbonate is ammonium acetate.  
   
   
       7 . The process according to the  claim 3  or  4 , wherein the reaction of ethyl 3,4-bis(2-methoxyethoxy)-benzoate with nitric acid in the presence of sulfuric acid is conducted at a temperature in the range of 45 to 75° C. to prepare ethyl 4,5-bis(2-methoxyethoxy)-2-nitrobenzoate.  
   
   
       8 . The process according to the  claim 3  or  4 , wherein the metallic catalyst comprises 1 to 2.9 wt. % of platinum carried on a carbon carrier.