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′-bromomethyl biphenyl-2-yl) tetrazole (250 g), potassium carbonate (170 g) & tetra butyl ammonium bromide (15 g) in acetone (2.5 L) were refluxed for 10-16 hours. Progress of reaction was monitor by HPLC. Reaction mass was cooled & filtered to remove the salts. Inorganic 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 (2000 ml) was added slowly to above solution at room temperature. Reaction mass was stir for 2-4 hrs at 30-40° C. Isopropyl alcohol was distilled under reduced pressure. Water (I 000 ml), sodium chloride (100 g) & ethyl acetate (2000 ml) was added to the residue. Separate the two layers & aqueous layer was extracted with ethyl acetate (3×1000 ml). Combined ethyl acetate layer was washed with sodium bicarbonate solution (2×2000 ml) & dried (Na2SO4). Distilled off ethyl acetate under reduced pressure completely. Add acetonitrile (2000 ml) was added to the residue. The reaction mass was cooled, filtered, washed with acetonitrile (500 ml) & dried to get 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(trityltetrazol-5-yl)phenyl]phenyl}methylimidazole-5-carboxylic acid dihydrate (250 g).

1. customProgress of reaction
2. customReaction mass
3. temperaturewas cooled
4. filtrationfiltered
5. customto remove the salts
6. washInorganic salts were washed with acetone (300 ml)
7. distillationAcetone from combine the filtrate & washings was distilled
8. customThe residue obtained
9. temperatureThe reaction mass was cooled
10. filtrationfiltered
11. filtrationsolid after filtration
12. dissolutionwas dissolved in Isopropyl alcohol (1500 ml)
13. additionSeparately prepared solution of potassium hydroxide (180 g) in IPA (2000 ml) was added slowly to above solution at room temperature
14. customReaction mass
15. distillationIsopropyl alcohol was distilled under reduced pressure
16. additionWater (I 000 ml), sodium chloride (100 g) & ethyl acetate (2000 ml) was added to the residue
17. customSeparate the two layers & aqueous layer
18. extractionwas extracted with ethyl acetate (3×1000 ml)
19. washCombined ethyl acetate layer was washed with sodium bicarbonate solution (2×2000 ml)
20. dry with materialdried (Na2SO4)
21. distillationDistilled off ethyl acetate under reduced pressure completely
22. additionAdd acetonitrile (2000 ml) was added to the residue
23. temperatureThe reaction mass was cooled
24. filtrationfiltered
25. washwashed with acetonitrile (500 ml)
26. customdried