Potassium Iodide → HCID 178440075, compound

HRID 554015Notes

Reaction equation

HRID 554015 reaction equation
O.O.[OH:3][C:4]([C:7]1[N:8]=[C:9]([CH2:52][CH2:53][CH3:54])[N:10]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[C:28]3[N:32](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:31]=[N:30][N:29]=3)=[CH:18][CH:17]=2)[C:11]=1[C:12]([OH:14])=[O:13])([CH3:6])[CH3:5].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Cl[CH2:64][C:65]1[O:66][C:67](=[O:71])[O:68][C:69]=1[CH3:70]>CC(C)=O>[CH3:54][CH2:53][CH2:52][C:9]1[N:10]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[C:28]3[NH:32][N:31]=[N:30][N:29]=3)=[CH:18][CH:17]=2)[C:11]([C:12]([O:14][CH2:70][C:69]2[O:68][C:67](=[O:71])[O:66][C:65]=2[CH3:64])=[O:13])=[C:7]([C:4]([OH:3])([CH3:6])[CH3:5])[N:8]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 98555184-(Chloromethyl)-5-methyl-1,3-dioxol-2-oneHCID 67459182HCID 67459182, compound

Product 1

HCID 178440075HCID 178440075, compoundYield 77.9%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Conditions

Temperature
-12.5 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-6e26a519548844a6b6ab07fbeeb291e2
Source dataset
uspto-grants-2011_11
Patent number
US08048904B2

Reaction notes

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