Hydrochloric Acid → HCID 178467377, compound

HRID 1901978Notes

Reaction equation

HRID 1901978 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].CO.Cl.C(=O)([O-])O.[Na+]>C(Cl)Cl.C(OCC)(=O)C.O>[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

8

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 516892Sodium BicarbonateHCID 11029254Trityl candesartan cilexetil

Product 1

HCID 178467377HCID 178467377, compoundYield 75%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

In 15 mL of methylene chloride was dissolved 5.44 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 54 mL of methanol and 8.2 mL of 1N-HCl, and the mixture was stirred at 25° C. for 2 hours. Then, 19 mL of water and 19 mL of ethyl acetate were added and the mixture was adjusted to pH 3.2 with a saturated aqueous solution of sodium hydrogen carbonate. The mixture was extracted using 19 mL of water and 54 mL of ethyl acetate and the aqueous layer was separated and extracted with 30 mL of ethyl acetate. The organic layers were combined, washed with 40 mL of water and concentrated under reduced pressure to give an oil. This oil was purified by silica gel chromatography (300 mL, methylene chloride-methanol=10:1) to provide 2.92 g of (±)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methylbenzimidazole-7-carboxylate (yield 75%).

Workup

  1. extractionThe mixture was extracted
  2. customthe aqueous layer was separated
  3. extractionextracted with 30 mL of ethyl acetate
  4. washwashed with 40 mL of water
  5. concentrationconcentrated under reduced pressure
  6. customto give an oil
  7. customThis oil was purified by silica gel chromatography (300 mL, methylene chloride-methanol=10:1)

Sources & evidence

ORD record
ord-1809bf82ca494902a8684fd7accd8b47
Source dataset
uspto-grants-1996_11
Patent number
US05578733

Reaction notes

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