反应详情

温度

35 °C

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 combined filtrate was distilled completely & residue 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) & dried (Na2SO4). Toluene layer was filtered & cooled to 0 to −20° C. Conc. HCl (1.35 L) was added slowly to above reaction mass at −5 to −15° C. Stirred for 1 hr. The two layers were separated & ethyl acetate (3.0 L) was added to aqueous layer. The pH of combined layers was adjusted to 5.0-6.5 by adding potassium carbonate solution. Both the layers were separated (Store the ethyl acetate layer-containing compound) & aqueous layer was extracted with ethyl acetate (3×2.0 L). Combined organic layers were washed with brine. Ethyl acetate was distilled from organic layer containing compound under reduced pressure. The residue was dissolved in acetone (2.5 to 4 Lt) at reflux temperature. The solution was stirred with carbon & filtered, followed by partial distillation of acetone. The reaction mass was cooled slowly to 0-5° C. Filtered, washed with acetone (2×200 ml) & dried to get Olmesartan

1. temperatureThe reaction mass was cooled
2. filtrationfiltered
3. customto remove the salts
4. washSalts were washed with acetone (300 ml)
5. distillationAcetone from combined filtrate was distilled completely
6. temperatureresidue was refluxed with acetonitrile (500 ml)
7. temperatureThe reaction mass was cooled
8. filtrationfiltered
9. filtrationsolid after filtration
10. dissolutionwas dissolved in isopropyl alcohol (1500 ml)
11. additionSeparately prepared solution of potassium hydroxide (180 g) in IPA (2.0 L) was added to above solution at room temperature
12. customReaction
13. distillationIsopropyl alcohol was distilled under reduced pressure
14. additionBrine (1.0 L) & ethyl acetate (2.0 L) was added to the residue
15. customAfter layer separation aqueous layer
16. extractionwas extracted with ethyl acetate (3×1000 ml)
17. washCombined ethyl acetate layer was washed with sodium bicarbonate solution (2×2.0 L)
18. dry with materialdried (Na2SO4)
19. distillationEthyl acetate was distilled completely under reduced pressure
20. additionAcetone (4.0 L) was added to the residue
21. temperatureheated to reflux
22. customthe solution obtained
23. temperatureat reflux temperature
24. customReaction, mass
25. temperaturewas refluxed for 2-6 hrs
26. customAfter competition of reaction
27. filtrationthe reaction mass was filtered
28. distillationthe acetone was distilled
29. customThe residue obtained
30. washwas washed with brine (3×750 ml)
31. dry with materialdried (Na2SO4)
32. filtrationToluene layer was filtered
33. temperaturecooled to 0 to −20° C
34. additionConc. HCl (1.35 L) was added slowly to above reaction mass at −5 to −15° C
35. stirringStirred for 1 hr
36. customThe two layers were separated
37. additionethyl acetate (3.0 L) was added to aqueous layer
38. additionby adding potassium carbonate solution
39. customBoth the layers were separated (Store the ethyl acetate layer-containing compound) & aqueous layer
40. extractionwas extracted with ethyl acetate (3×2.0 L)
41. washCombined organic layers were washed with brine
42. distillationEthyl acetate was distilled from organic layer
43. additioncontaining compound under reduced pressure
44. dissolutionThe residue was dissolved in acetone (2.5 to 4 Lt)
45. temperatureat reflux temperature
46. stirringThe solution was stirred with carbon
47. filtrationfiltered
48. distillationfollowed by partial distillation of acetone
49. temperatureThe reaction mass was cooled slowly to 0-5° C
50. filtrationFiltered
51. washwashed with acetone (2×200 ml)
52. customdried