反应详情

温度

-12.5 °C

4-(1-hydroxy-1-Methylethyl)-2-propyl-1-{4-[2-(trityltetrazol-5-yl)phenyl]phenyl}methyl imidazole-5-carboxylic acid dihydrate (250 g) in acetone (4000 ml) 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. Progress of reaction was monitor by HPLC. After completion of reaction mass was filtered, distilled the acetone from filtrate & dissolved the residue obtained in toluene (2500 ml). Toluene layer was washed with brine & dried (Na2SO4). Toluene layer was filtered & cooled to −5 to −20° C. Conc hydrochloric acid (600 ml) was added slowly to above reaction mass at −5 to −20° C. & Stir for 1 hr at −5 to −20° C. Separated the two layers. Ethyl acetate (3000 ml) was added to aqueous layer. The pH of combined layers was adjusted to 5.0-6.5 by slowly adding potassium carbonate solution. Both the layers were separated (Store the ethyl acetate layer containing compound). Aqueous layer was extracted with ethyl acetate (3×2000 ml). The combined organic layer was washed with brine. Ethyl acetate was partially distilled (about 85% of original volume) from organic layer containing compound under reduced pressure. Reaction mass was cooled, filtered, washed with ethyl acetate (3×200 ml) & dried to get Olmesartan Medoxomil (150 g).

1. temperatureat reflux temperature
2. customReaction mass
3. temperaturewas refluxed for 2-6 hrs
4. customProgress of reaction
5. customAfter completion of reaction mass
6. filtrationwas filtered
7. distillationdistilled the acetone from filtrate
8. dissolutiondissolved the residue
9. customobtained in toluene (2500 ml)
10. washToluene layer was washed with brine
11. dry with materialdried (Na2SO4)
12. filtrationToluene layer was filtered
13. additionConc hydrochloric acid (600 ml) was added slowly to above reaction mass at −5 to −20° C.
14. customSeparated the two layers
15. additionEthyl acetate (3000 ml) was added to aqueous layer
16. customBoth the layers were separated (Store the ethyl acetate layer
17. additioncontaining compound)
18. extractionAqueous layer was extracted with ethyl acetate (3×2000 ml)
19. washThe combined organic layer was washed with brine
20. distillationEthyl acetate was partially distilled (about 85% of original volume) from organic layer
21. additioncontaining compound under reduced pressure
22. customReaction mass
23. temperaturewas cooled
24. filtrationfiltered
25. washwashed with ethyl acetate (3×200 ml)
26. customdried