Dimethylformamide → 2-chloro-1-(2-ethoxyethyl)-1H-benzimidazole

HRID 637015Notes

Reaction equation

HRID 637015 reaction equation
[Cl:1][C:2]1[NH:6][C:5]2[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=2[N:3]=1.CN(C)C=O.[H-].[Na+].[CH2:18]([O:20][CH2:21][CH2:22]Cl)[CH3:19]>C(OCC)(=O)C.CCCCCC.C(OCC)(=O)C>[Cl:1][C:2]1[N:6]([CH2:19][CH2:18][O:20][CH2:21][CH3:22])[C:5]2[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=2[N:3]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 12341Ethane, 1-chloro-2-ethoxy-HCID 24758Sodium hydrideHCID 785722-Chlorobenzimidazole

Product 1

HCID 104893562-chloro-1-(2-ethoxyethyl)-1H-benzimidazole

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21226206Ethyl acetate hexaneSolvent2×

Conditions

Temperature
60 °C

Procedure

Combine 2-chloro-1H-benzimidazole (21.1.4 g, 138.4 mmol) and dimethylformamide (200 mL). Add portionwise, sodium hydride (24.0 g, 60% in oil, 153.3 mmol). After 15 minutes, add 2-chloroethyl ethyl ether (21.9 g, 201,5 mmol). Heat to 60° C. After 18 hours, cool the reaction mixture and dilute with ethyl acetate. Extract with a saturated aqueous sodium bicarbonate solution, water, and then brine. Dry the organic layer over MgSO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting sequentially with 10% ethyl acetate/hexane and then 30% ethyl acetate hexane to give the 2-chloro-1-(2-ethoxyethyl)-1H-benzimidazole: Rf=0.74 (silica gel, 7/3 ethyl acetate/hexane).

Workup

  1. additionAdd portionwise
  2. waitAfter 18 hours
  3. temperaturecool the reaction mixture
  4. extractionExtract with a saturated aqueous sodium bicarbonate solution, water
  5. dry with materialDry the organic layer over MgSO4
  6. filtrationfilter
  7. customevaporate in vacuo
  8. customto give a residue

Sources & evidence

ORD record
ord-eeaf591ddeb7407dbd3876cc0b8f27de
Source dataset
uspto-grants-2001_02
Patent number
US06194406B1

Reaction notes

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