Dimethylformamide → 4-(1H-benzoimidazol-2-ylmethoxy)-2-chloro-5-methoxy-benzaldehyde

HRID 253455

Reaction equation

HRID 253455 reaction equation
[Cl: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>>[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]([Cl:1])[CH:9]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 290002-Chloro-4-hydroxy-5-methoxybenzaldehydeHCID 598038544-(1H-benzoimidazol-2-ylmethoxy)-5-chloro-2-fluoro-benzaldehyde

Product 1

HCID 598038904-(1H-benzoimidazol-2-ylmethoxy)-2-chloro-5-methoxy-benzaldehyde

Conditions

Temperature
80 °C

Procedure

2-Chloro-4-hydroxy-5-methoxy-benzaldehyde (136, 2.30 g, 0.0123 mol) was dissolved in N,N-dimethylformamide (89.5 mL, 1.16 mol) and sodium hydride (60% dispersion in mineral oil, 541 mg, 0.0135 mol) was added. After 20 minutes, 2-chloromethyl-1H-benzoimidazole (106, 2.05 g, 0.0123 mol) was added to the reaction. The reaction was stirred at 80° C. overnight. The reaction was concentrated in vacuo to an oil. Ethyl acetate was added and washed with saturated sodium bicarbonate and brine. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 30-70% ethyl acetate in hexane over 30 minutes to provide a white solid (137, 1.79 g, 46%). MS (ESI) [M+H+]+=317.1, 319.1.

Workup

  1. concentrationThe reaction was concentrated in vacuo to an oil
  2. additionEthyl acetate was added
  3. washwashed with saturated sodium bicarbonate and brine
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. custompurified by silica gel column chromatography
  8. washeluting with 30-70% ethyl acetate in hexane over 30 minutes
  9. customto provide a white solid (137, 1.79 g, 46%)

Sources & evidence

ORD record
ord-fc39b84c238541d1868b16b5ef595e9e
Source dataset
uspto-grants-2011_01
Patent number
US07872018B2

Linked notes

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