Candesartan

139481-69-9

139481-59-7

The general procedure for the synthesis of 1-((2'-(2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-2-ethoxy-1-[[(2'-(1H-tetrazol-5-yl)biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylic acid using 2-ethoxy-1-[[(2'-(1H-tetrazol-5-yl)biphenyl]-4-yl)methyl]-2-ethoxy-1H-benzo[d]imidazole-7-carboxylic acid was performed as follows: the obtained in step A) was product (350 g) was dissolved in methanol (1.17 L), followed by addition of sodium hydroxide solution (93 g, dissolved in 1.17 L of water). The reaction mixture was heated to 78-80°C and refluxed for 1 hour. After completion of the reaction, methanol was removed under vacuum at 40-45°C. Ethyl acetate (2.8 L) and water (3.50 L) were added to the residue, stirred for 1 hour at room temperature and allowed to stand for 15 minutes. The organic and aqueous layers were separated, and the pH of the aqueous layer was adjusted to 4-5 with acetic acid (~450 g) at a controlled temperature of 10-15°C. The product was extracted by filtration. The precipitated product was filtered, washed twice with water (2 x 0.7 L) and blotted dry. The wet filter cake was air-dried at room temperature for 2 h and then dried at 50-55 °C to afford the target product 1-((2'-(2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylic acid in 323 g (95% yield).