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Water → 3-({6-[(5-bromo-6-methoxypyridin-2-yl)oxy]-1-methyl-1H-benzimidazol-2-yl}methoxy)benzoic acid

HRID 1843697
Notes
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Reaction equation

HRID 1843697 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:9][C:10]2[CH:11]=[CH:12][C:13]3[N:17]=[C:16]([CH2:18][O:19][C:20]4[CH:21]=[C:22]([CH:27]=[CH:28][CH:29]=4)[C:23](OC)=[O:24])[N:15]([CH3:30])[C:14]=3[CH:31]=2)=[N:6][C:7]=1Cl.[CH3:32][O-:33].[Na+].[OH2:35]>O1CCOCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:9][C:10]2[CH:11]=[CH:12][C:13]3[N:17]=[C:16]([CH2:18][O:19][C:20]4[CH:21]=[C:22]([CH:27]=[CH:28][CH:29]=4)[C:23]([OH:35])=[O:24])[N:15]([CH3:30])[C:14]=3[CH:31]=2)=[N:6][C:7]=1[O:33][CH3:32]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 962WaterHCID 10942334Sodium MethoxideHCID 86661626Methyl 3-({6-[(5-bromo-6-chloropyridin-2-yl)oxy]-1-methyl-1H-benzimidazol-2-yl}methoxy)benzoate

Product 1

HCID 667058413-({6-[(5-bromo-6-methoxypyridin-2-yl)oxy]-1-methyl-1H-benzimidazol-2-yl}methoxy)benzoic acid

Reagents, catalysts & solvents 1

HCID 312751,4-Dioxane
Solvent

Procedure

Methyl 3-({6-[(5-bromo-6-chloropyridin-2-yl)oxy]-1-methyl-1H-benzimidazol-2-yl}methoxy)benzoate produced in Example (3a) (0.74 g, 1.47 mmol), sodium methoxide (5.0 M solution in methanol, 2.94 mL, 14.7 mmol), water (10 mL) and 1,4-dioxane (20 mL) were stirred with heating under reflux for three days. After leaving to cool, the reaction mixture was concentrated and water (50 mL) was added. This aqueous solution was neutralized by adding 1 M hydrochloric acid and the precipitated solid was collected by filtration to obtain crude 3-({6-[(5-bromo-6-methoxypyridin-2-yl)oxy]-1-methyl-1H-benzimidazol-2-yl}methoxy)benzoic acid. Trimethylsilyldiazomethane (2.0 M solution in hexane) was added to a solution of the crude 3-({6-[(5-bromo-6-methoxypyridin-2-yl)oxy]-1-methyl-1H-benzimidazol-2-yl}methoxy)benzoic acid in toluene (20 mL) and methanol (10 mL) until the raw material disappeared. The reaction mixture was concentrated under reduced pressure. Then, the residue was purified by silica gel chromatography (hexane/ethyl acetate, 1:1) to obtain the title compound (0.36 g, 49%) as a white solid.

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for three days
  3. customAfter leaving
  4. temperatureto cool
  5. concentrationthe reaction mixture was concentrated
  6. additionwater (50 mL) was added
  7. additionby adding 1 M hydrochloric acid
  8. filtrationthe precipitated solid was collected by filtration

Sources & evidence

ORD record
ord-0d45454afcef4f3ab9a16928b22df5c4
Source dataset
uspto-grants-2015_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08946264B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes