Hydrochloric Acid → pivaloyloxymethyl 2-ethoxy-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methylbenzimidazole-7-carboxylate

HRID 963679Notes

Reaction equation

HRID 963679 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][CH2:53][O:54][C:55](=[O:60])[C:56]([CH3:59])([CH3:58])[CH3:57])=[O:51])=[CH:47][CH:48]=[CH:49][C:6]=2[N:5]=1)[CH3:2].Cl.C(=O)([O-])O.[Na+]>C(Cl)Cl.CO.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:26][N:25]=[N:24][N:23]=3)=[CH:14][CH:15]=2)[C:7]2[C:46]([C:50]([O:52][CH2:53][O:54][C:55](=[O:60])[C:56]([CH3:59])([CH3:58])[CH3:57])=[O:51])=[CH:47][CH:48]=[CH:49][C:6]=2[N:5]=1)[CH3:2]

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 19083195pivaloyloxymethyl 2-ethoxy-1-[2'-(N-triphenylmethyl-1H-tetrazol-5-yl)biphenyl-4-yl]methylbenzimidazole-7-carboxylate

Product 1

HCID 178467381pivaloyloxymethyl 2-ethoxy-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methylbenzimidazole-7-carboxylateYield 91%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
5 °C

Procedure

In a mixture of 17 mL of methylene chloride and 13 mL of methanol was dissolved 5.79 g of pivaloyloxymethyl 2-ethoxy-1-[2'-(N-triphenylmethyl-1H-tetrazol-5-yl)biphenyl-4-yl]methylbenzimidazole-7-carboxylate and the solution was cooled to 5° C. To this solution was added 3.7 mL of methanol containing 0.344 g of hydrogen chloride dropwise and the mixture was stirred at 5°-6° C. for 2 hours. Then, 11 mL of ethyl acetate and 11 mL of water were added and the mixture was adjusted to pH 6.2 with a saturated aqueous solution of sodium hydrogen carbonate. Then, 6 mL of ethyl acetate and 20% NaCl--H2O were added. The aqueous layer was taken and extracted with 12 mL of ethyl acetate. The organic layers were combined and redistributed into 22 mL of ethyl acetate and 20% NaCl solution. The organic layer was separated and concentrated and the residue was stirred in 15 mL of toluene at room temperature for 30 minutes. Then, 100 mL of hexane was added and the mixture was stirred under ice-cooling for 1 hour. The resulting crystals were collected by filtration, washed with 20 mL of toluene-hexane (1:9), and dried to provide 3.65 g of pivaloyloxymethyl 2-ethoxy-1-[2'-(1H-tetrazol-5-yl)-biphenyl-4-yl]methylbenzimidazole-7-carboxylate (yield 91%).

Workup

  1. extractionextracted with 12 mL of ethyl acetate
  2. customThe organic layer was separated
  3. concentrationconcentrated
  4. stirringthe residue was stirred in 15 mL of toluene at room temperature for 30 minutes
  5. additionThen, 100 mL of hexane was added
  6. stirringthe mixture was stirred under ice-
  7. temperaturecooling for 1 hour
  8. filtrationThe resulting crystals were collected by filtration
  9. washwashed with 20 mL of toluene-hexane (1:9)
  10. customdried

Sources & evidence

ORD record
ord-3879f27a5c80485da05689b18440da9a
Source dataset
uspto-grants-1998_06
Patent number
US05763619

Reaction notes

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