Ethyl bromoacetate → Ethyl {[1-[(4-chlorophenyl)methyl]-2-(1-methylethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-7-yl]oxy}acetate

HRID 1946524Notes

Reaction equation

HRID 1946524 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:13]3[CH:14]([OH:18])[CH2:15][CH2:16][CH2:17][C:12]=3[N:11]=[C:10]2[CH:19]([CH3:21])[CH3:20])=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][N:9]2[C:13]3[CH:14]([O:18][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:15][CH2:16][CH2:17][C:12]=3[N:11]=[C:10]2[CH:19]([CH3:21])[CH3:20])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 584601861-[(4-chlorophenyl)methyl]-2-(1-methylethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-7-ol

Product 1

HCID 58460188Ethyl {[1-[(4-chlorophenyl)methyl]-2-(1-methylethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-7-yl]oxy}acetate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of Intermediate 58 (55 mg) in anhydrous tetrahydrofuran (3 mL) at 0° C. under an atmosphere of nitrogen was added sodium hydride (10 mg) as a 60% by weight suspension on mineral oil in one charge. The reaction was stirred at 0° C. for 30 min. To the reaction was added neat ethyl bromoacetate (0.026 mL) in one charge the reaction was then allowed to warm to ambient temperature under an atmosphere of nitrogen over 30 min. The reaction was quenched with saturated aqueous ammonium chloride (5 mL) and extracted with ethyl acetate (10 mL). The extract was dried (hydrophobic frit) and concentrated in vacuo. The sample was loaded in dichloromethane and purified on silica using a 0-25% methanol-dichloromethane gradient. The appropriate fractions were combined and evaporated in vacuo to provide the title compound (14 mg). LC/MS MH+ 391, Rt 1.84 min (5 min run).

Workup

  1. additioncharge
  2. additioncharge the reaction
  3. temperatureto warm to ambient temperature under an atmosphere of nitrogen over 30 min
  4. customThe reaction was quenched with saturated aqueous ammonium chloride (5 mL)
  5. extractionextracted with ethyl acetate (10 mL)
  6. customThe extract was dried (hydrophobic frit)
  7. concentrationconcentrated in vacuo
  8. custompurified on silica using a 0-25% methanol-dichloromethane gradient
  9. customevaporated in vacuo

Sources & evidence

ORD record
ord-ee29ab1c8be048bb9b72f594dc2fec89
Source dataset
uspto-grants-2013_03
Patent number
US08399444B2

Reaction notes

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