Benzyl Bromide → ethyl 3-(1-benzyl-1H-benzo[d]imidazol-2-yl)propanoate

HRID 2059963Notes

Reaction equation

HRID 2059963 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][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13].[H-].[Na+].[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>O1CCCC1>[CH2:19]([N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 2281351h-Benzimidazole-2-propanoic acid, ethyl ester

Product 1

HCID 59432964ethyl 3-(1-benzyl-1H-benzo[d]imidazol-2-yl)propanoateYield 82.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of ethyl 3-(1H-benzo[d]imidazol-2-yl)propanoate 6a (2.85 g, 13.1 mmol, 1.0 eq.) in tetrahydrofuran (100 mL) at 0° C., was added 60% sodium hydride in mineral oil (784 mg, 19.6 mmol, 1.5 eq.), and the reaction was stirred at 0° C. for 20 minutes. Benzyl bromide (4.47 g, 26.1 mmol, 2.0 eq.) was added at 0° C., and the reaction was stirred, with warming to room temperature, for 16 hours. The mixture was concentrated in vacuo and water (100 mL) was carefully added. The aqueous layer was extracted with dichloromethane (3×75 mL), and the combined organic extracts were washed with 1M hydrochloric acid (100 mL) and brine (100 mL). The organic layer was dried over magnesium sulfate and concentrated in vacuo. Purification by flash chromatography (5% MeOH:95% EtOAc) gave 6b as an orange oil (3.32 g, 82%).

Workup

  1. stirringthe reaction was stirred
  2. temperaturewith warming to room temperature, for 16 hours
  3. concentrationThe mixture was concentrated in vacuo and water (100 mL)
  4. additionwas carefully added
  5. extractionThe aqueous layer was extracted with dichloromethane (3×75 mL)
  6. washthe combined organic extracts were washed with 1M hydrochloric acid (100 mL) and brine (100 mL)
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customPurification by flash chromatography (5% MeOH:95% EtOAc)

Sources & evidence

ORD record
ord-2955c2cfed22477e8197f5d809939748
Source dataset
uspto-grants-2012_10
Patent number
US08278327B2

Reaction notes

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