Potassium Iodide → Tritylolmesartan medoxomil

Participants

Reaction Conditions

Reaction Steps

4-(1-Hydroxy-1-methylethyl)-2-Propyl-1H-imidazole-5-carboxylic acid ethyl ester (100 g), N-(triphenylmethyl)-5 (4′-bromomethylbiphenyl-2-yl)tetrazole (250 g), potassium carbonate (170 g) & tetra butyl ammonium bromide (15 g) in acetone (2.5 L) were refluxed for 15 hours. The reaction mass was cooled & filtered to remove the salts. Salts were washed with acetone (300 ml). Acetone from combine the filtrate & washings was distilled. The residue obtained was refluxed with acetonitrile (500 ml). The reaction mass was cooled, filtered & solid after filtration was dissolved in Isopropyl alcohol (1500 ml). Separately prepared solution of potassium hydroxide (180 g) in IPA (2.0 L) was added to above solution at room temperature. Reaction was stirred for 3 hrs at 30-40° C. Isopropyl alcohol was distilled under reduced pressure. Brine (1.0 L) & ethyl acetate (2.0 L) was added to the residue. After layer separation aqueous layer was extracted with ethyl acetate (3×1000 ml). Combined ethyl acetate layer was washed with sodium bicarbonate solution (2×2.0 L) & dried (Na2SO4). Ethyl acetate was distilled completely under reduced pressure. Acetone (4.0 L) was added to the residue & heated to reflux; the solution obtained was added to suspension of potassium carbonate (50 g), potassium iodide (15 g) & 4-chloromethyl-5-methyl-1,3-dioxol-2-one (75 g) in acetone (1500 ml) at reflux temperature. Reaction mass was refluxed for 2-6 hrs. After competition of reaction, the reaction mass was filtered & the acetone was distilled from combined mother liquor. The residue obtained was dissolved in toluene (2.5 L) toluene layer was washed with brine (3×750 ml) Toluene was removed under reduced pressure. Methanol (1.5 L) was added to the residue and stirred at 35° C. for 2 hr. Reaction mass was cooled to 0° C., filtered, washed with (2×500 ml) chilled methanol & dried to get pure Trityl Olmesartan Medoxomil (200 g)

Provenance & Evidence