Sodium Hydroxide → 4-((1H-benzo[d]imidazol-2-yl)methyl)benzoic acid

HRID 1163091Notes

Reaction equation

HRID 1163091 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][C:11]1[CH:20]=[CH:19][C:14]([C:15]([O:17]C)=[O:16])=[CH:13][CH:12]=1.[OH-].[Na+]>CO>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][C:11]1[CH:20]=[CH:19][C:14]([C:15]([OH:17])=[O:16])=[CH:13][CH:12]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 59468704methyl 4-((1H-benzo[d]imidazol-2-yl)methyl)benzoate

Product 1

HCID 190232394-((1H-benzo[d]imidazol-2-yl)methyl)benzoic acidYield 92%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of methyl 4-((1H-benzo[d]imidazol-2-yl)methyl)benzoate (400 mg, 1.5 mmol) in methanol was treated with aqueous sodium hydroxide (2.5 M, 3.75 mmol), heated at reflux temperature for 3 h and concentrated in vacuo. The resultant residue was dispersed in water and acidified with excess formic acid. The resultant precipitate was removed by filtration, washed with water and dried under vacuum overnight to provide 4-((1H-benzo[d]imidazol-2-yl)methyl)benzoic acid (92%) as a white solid, [M+H] 253.2. A solution of 4-((1H-benzo[d]imidazol-2-yl)methyl)benzoic acid (200 mg, 0.79 mmol) in DMF was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (183 mg, 0.952 mmol) and 1-hydroxybenzotriazole (134 mg, 0.873 mmol), stirred at room temperature for 3 h, treated with a solution of (3′S)-1,3′-bipyrrolidine (166.6 mg, 1.19 mmol) in DMF, stirred at room temperature for 6 h and concenrated in vacuo. This residue was partitioned between aqueous potassium carbonate (1.0 M) and dichloromethane. The organic phase was washed with water, dried over sodium sulfate and concentrated under reduced pressure. Purification of the concentrate by flash column chromatography (silica, dichloromethane:methanol 20:1 to 10:1) afforded the title compound (73%), identified by mass spectral analysis. [M+H] 253.2.

Workup

  1. temperatureheated
  2. temperatureat reflux temperature for 3 h
  3. concentrationconcentrated in vacuo
  4. additionThe resultant residue was dispersed in water
  5. customThe resultant precipitate was removed by filtration
  6. washwashed with water
  7. customdried under vacuum overnight

Sources & evidence

ORD record
ord-0ad1568186ed4cdda271f4283a078006
Source dataset
uspto-grants-2010_10
Patent number
US07820825B2

Reaction notes

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