Potassium Iodide → Tritylolmesartan medoxomil

Temperature

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 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)

1. temperatureThe reaction mass was cooled
2. filtrationfiltered
3. customto remove the salts
4. washSalts were washed with acetone (300 ml)
5. distillationAcetone from combine the filtrate & washings was distilled
6. customThe residue obtained
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) Toluene
31. customwas removed under reduced pressure
32. additionMethanol (1.5 L) was added to the residue
33. stirringstirred at 35° C. for 2 hr
34. customReaction mass
35. temperaturewas cooled to 0° C.
36. filtrationfiltered
37. washwashed with (2×500 ml)
38. temperaturechilled methanol
39. customdried

ORD record

ord-8e727997aa5543d0b13ed1772526cead

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08048904B2