Hydrochloric Acid → HCID 178467377, compound

HRID 1901975Notes

Reaction equation

HRID 1901975 reaction equation
[CH2:1]([O:3][C:4]1[N:8]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]3[N:26](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:25]=[N:24][N:23]=3)=[CH:12][CH:11]=2)[C:7]2[C:46]([C:50]([O:52][CH:53]([O:55][C:56]([O:58][CH:59]3[CH2:64][CH2:63][CH2:62][CH2:61][CH2:60]3)=[O:57])[CH3:54])=[O:51])=[CH:47][CH:48]=[CH:49][C:6]=2[N:5]=1)[CH3:2].Cl.C(=O)([O-])O.[Na+].[Na+].[Cl-].O>C(Cl)Cl.C(OCC)(=O)C.O.CO>[CH2:1]([O:3][C:4]1[N:8]([CH2:9][C:10]2[CH:11]=[CH:12][C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]3[NH:23][N:24]=[N:25][N:26]=3)=[CH:14][CH:15]=2)[C:7]2[C:46]([C:50]([O:52][CH:53]([O:55][C:56]([O:58][CH:59]3[CH2:60][CH2:61][CH2:62][CH2:63][CH2:64]3)=[O:57])[CH3:54])=[O:51])=[CH:47][CH:48]=[CH:49][C:6]=2[N:5]=1)[CH3:2]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 11029254Trityl candesartan cilexetilHCID 57417360Sodium chloride; water

Product 1

HCID 178467377HCID 178467377, compoundYield 96.4%

Reagents, catalysts & solvents 4

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
5 °C

Procedure

In 29 mL of methylene chloride was dissolved 10.00 g of (±)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[2'-(N-triphenylmethyl-1H-tetrazol-5-yl)biphenyl-4-yl]methylbenzimidazole-7-carboxylate followed by addition of 23 mL of methanol and cooling to 5° C. Then, 6 mL of methanol containing 0.53 g of hydrogen chloride as dissolved was added dropwise at 5° C. over a period of 15 minutes. The mixture was further stirred at 5° C. for 3.5 hours, at the end of which time 19 mL of ethyl acetate and 19 mL of water were added. The mixture was adjusted to pH 6.3 with a saturated aqueous solution of sodium hydrogen carbonate and, then, 10 mL of ethyl acetate and 10 mL of 20% NaCl-H2O were added. The aqueous layer was separated and extracted with 20 mL of ethyl acetate. The ethyl acetate layers were combined and redistributed into 20% NaCl and 38 mL of ethyl acetate. The organic layer was separated and concentrated and the residue was diluted with ethanol and reconcentrated. To the residue was added 20 mL of acetone and the mixture was stirred at room temperature for 3 hours for sufficient crystallization. Thereafter, 90 mL of hexane was added and the mixture was further stirred at room temperature for 1 hour and, then, under ice-cooling for 2 hours. The resulting crystals were collected by filtration and washed with 25 mL of acetone-hexane (1:9). The crystals were dried under reduced pressure to provide 6.90 g of (±)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methylbenzimidazole-7-carboxylate (yield 92%).

Workup

  1. additionwas added dropwise at 5° C. over a period of 15 minutes
  2. additionwere added
  3. customThe aqueous layer was separated
  4. extractionextracted with 20 mL of ethyl acetate
  5. customThe organic layer was separated
  6. concentrationconcentrated
  7. additionthe residue was diluted with ethanol
  8. additionTo the residue was added 20 mL of acetone
  9. additionThereafter, 90 mL of hexane was added
  10. stirringthe mixture was further stirred at room temperature for 1 hour
  11. temperatureunder ice-cooling for 2 hours
  12. filtrationThe resulting crystals were collected by filtration
  13. washwashed with 25 mL of acetone-hexane (1:9)
  14. customThe crystals were dried under reduced pressure

Sources & evidence

ORD record
ord-0e17169329214c57a216003015ceedae
Source dataset
uspto-grants-1996_11
Patent number
US05578733

Reaction notes

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