Trimethylsilyldiazomethane → Methyl 3-({6-[(5-bromo-6-methoxypyridin-2-yl)oxy]-1-methyl-1H-benzimidazol-2-yl}methoxy)benzoate

HRID 1843698Notes

Reaction equation

HRID 1843698 reaction equation
[CH3:1][Si](C=[N+]=[N-])(C)C.[Br:8][C:9]1[CH:10]=[CH:11][C:12]([O:17][C:18]2[CH:19]=[CH:20][C:21]3[N:25]=[C:24]([CH2:26][O:27][C:28]4[CH:29]=[C:30]([CH:34]=[CH:35][CH:36]=4)[C:31]([OH:33])=[O:32])[N:23]([CH3:37])[C:22]=3[CH:38]=2)=[N:13][C:14]=1[O:15][CH3:16]>C1(C)C=CC=CC=1.CO>[Br:8][C:9]1[CH:10]=[CH:11][C:12]([O:17][C:18]2[CH:19]=[CH:20][C:21]3[N:25]=[C:24]([CH2:26][O:27][C:28]4[CH:29]=[C:30]([CH:34]=[CH:35][CH:36]=4)[C:31]([O:33][CH3:1])=[O:32])[N:23]([CH3:37])[C:22]=3[CH:38]=2)=[N:13][C:14]=1[O:15][CH3:16]

Participants

5

Reactant 2

HCID 167693TrimethylsilyldiazomethaneHCID 667058413-({6-[(5-bromo-6-methoxypyridin-2-yl)oxy]-1-methyl-1H-benzimidazol-2-yl}methoxy)benzoic acid

Product 1

HCID 66705718Methyl 3-({6-[(5-bromo-6-methoxypyridin-2-yl)oxy]-1-methyl-1H-benzimidazol-2-yl}methoxy)benzoateYield 49%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

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. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customThen, the residue was purified by silica gel chromatography (hexane/ethyl acetate, 1:1)

Sources & evidence

ORD record
ord-2973977753a44b4c8a2784da570291a0
Source dataset
uspto-grants-2015_02
Patent number
US08946264B2

Reaction notes

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