Hydrogen Bromide → HCID 178440075, compound

HRID 2047265Notes

Reaction equation

HRID 2047265 reaction equation
[CH3:1][CH2:2][CH2:3][C:4]1[N:8]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[C:21]([C:22]4[N:26](C(C5C=CC=CC=5)(C5C=CC=CC=5)C5C=CC=CC=5)[N:25]=[N:24][N:23]=4)=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:12][CH:11]=2)[C:7]([C:46]([O:48][CH2:49][C:50]2[O:55][C:53](=[O:54])[O:52][C:51]=2[CH3:56])=[O:47])=[C:6]([C:57]([OH:60])([CH3:59])[CH3:58])[N:5]=1.Br>C1COCC1>[CH3:1][CH2:2][CH2:3][C:4]1[N:8]([CH2:9][C:10]2[CH:11]=[CH:12][C:13]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:21]=3[C:22]3[NH:26][N:25]=[N:24][N:23]=3)=[CH:14][CH:15]=2)[C:7]([C:46]([O:48][CH2:49][C:50]2[O:55][C:53](=[O:54])[O:52][C:51]=2[CH3:56])=[O:47])=[C:6]([C:57]([OH:60])([CH3:59])[CH3:58])[N:5]=1

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 19036162Tritylolmesartan medoxomil

Product 1

HCID 178440075HCID 178440075, compoundYield 99.68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

Trityl olmesartan medoxomil (250 g, 310 mmol) (97.3% area) is dissolved in THF (1560 ml) and 48 wt-% aqueous hydrobromic acid (70.6 ml, 625 mmol) is added slowly. The mixture is stirred for at 25° C. After 1 hour the precipitate forms. The mixture is stirred for 1 additional hour at 25° C., then cooled to −5° C. and stirred for 1.5 hours at −5° C. The precipitate is filtered. 940 ml of THF is added to the precipitate and the mixture is stirred for 1 h at 25° C. and then 1 hour at −5° C. Then precipitate is filtered off and washed with cold THF (150 ml). It is then dissolved in a mixture of water (875 ml) and acetone (440 ml). To a clear solution 5% aqueous solution of NaHCO3 is added to raise pH to 5.15. The mixture is stirred for 1 hour at room temperature and 1 hour at 0° C. The precipitate is filtered, washed with water and then recrystallised from a mixture of acetonitrile (280 ml) and water (70 ml) to give 124.5 g of olmesartan medoxomil (99.68% area).

Workup

  1. stirringThe mixture is stirred for 1 additional hour at 25° C.
  2. temperaturecooled to −5° C.
  3. stirringstirred for 1.5 hours at −5° C
  4. filtrationThe precipitate is filtered
  5. addition940 ml of THF is added to the precipitate
  6. stirringthe mixture is stirred for 1 h at 25° C.
  7. custom1 hour
  8. customat −5° C
  9. filtrationThen precipitate is filtered off
  10. washwashed with cold THF (150 ml)
  11. dissolutionIt is then dissolved in a mixture of water (875 ml) and acetone (440 ml)
  12. additionTo a clear solution 5% aqueous solution of NaHCO3 is added
  13. temperatureto raise pH to 5.15
  14. stirringThe mixture is stirred for 1 hour at room temperature and 1 hour at 0° C
  15. filtrationThe precipitate is filtered
  16. washwashed with water
  17. customrecrystallised from a mixture of acetonitrile (280 ml) and water (70 ml)

Sources & evidence

ORD record
ord-91a0bfa5244b413d9bff1f1d91085833
Source dataset
uspto-grants-2013_11
Patent number
US08592474B2

Reaction notes

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