Dimethylformamide → 4-(1H-benzimidazol-2-ylmethoxy)-2-fluoro-5-methoxy-benzaldehyde

HRID 253460

Reaction equation

HRID 253460 reaction equation
[F:1][C:2]1[CH:9]=[C:8]([OH:10])[C:7]([O:11][CH3:12])=[CH:6][C:3]=1[CH:4]=[O:5].CN(C)C=O.[H-].[Na+].[NH:20]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[N:22]=[C:21]1[CH2:29]OC1C(Cl)=CC(C=O)=C(F)C=1>O>[NH:20]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[N:22]=[C:21]1[CH2:29][O:10][C:8]1[C:7]([O:11][CH3:12])=[CH:6][C:3]([CH:4]=[O:5])=[C:2]([F:1])[CH:9]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 5981552-Fluoro-4-hydroxy-5-methoxybenzaldehydeHCID 598038544-(1H-benzoimidazol-2-ylmethoxy)-5-chloro-2-fluoro-benzaldehyde

Product 1

HCID 580860204-(1H-benzimidazol-2-ylmethoxy)-2-fluoro-5-methoxy-benzaldehydeYield 45.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

2-Fluoro-4-hydroxy-5-methoxy-benzaldehyde (39, 0.290 g, 1.7 mmol, prepared as described in Scheme 12 of Example 15) was dissolved in N,N-dimethylformamide (20 mL, 200 mmol). Sodium hydride (60% dispersion in oil, 0.852 g, 2.13 mmol) was added to the solution and after the mixture was stirred for 20 minutes at room temperature, 2-chloromethyl-1H-benzoimidazole (106, 0.28 g, 1.7 mmol) was added to the reaction. The obtained mixture was heated to 80° C. and stirred overnight. After cooling to room temperature, the reaction was poured into water and extracted with ethyl acetate. The organic portion was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with a gradient of ethyl acetate (40 to 100%) in hexane to give the desired compound (142, 0.233 g, 45%).

Workup

  1. temperatureThe obtained mixture was heated to 80° C.
  2. stirringstirred overnight
  3. temperatureAfter cooling to room temperature
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic portion was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated
  8. custompurified by silica gel column chromatography
  9. washeluting with a gradient of ethyl acetate (40 to 100%) in hexane

Sources & evidence

ORD record
ord-26eea312addc4aae9419fdc5fcd4839b
Source dataset
uspto-grants-2011_01
Patent number
US07872018B2

Linked notes

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