Dimethylformamide → 5-Benzyloxymethyl-2-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazole

HRID 408752Notes

Reaction equation

[Cl:1][C:2]1[N:6]([CH2:7][O:8][CH2:9][CH2:10][O:11][CH3:12])[C:5]2[CH:13]=[CH:14][C:15]([CH2:17][OH:18])=[CH:16][C:4]=2[N:3]=1.CN(C=O)C.[H-].[Na+].[CH2:26](Br)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>O>[CH2:26]([O:18][CH2:17][C:15]1[CH:14]=[CH:13][C:5]2[N:6]([CH2:7][O:8][CH2:9][CH2:10][O:11][CH3:12])[C:2]([Cl:1])=[N:3][C:4]=2[CH:16]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of [2-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-5-yl]-methanol (100 mg, 0.370 mmol) and DMF (3 mL) was added NaH (30.0 mg, 0.740 mmol, 60% suspension in mineral oil) at 0° C. The reaction mixture was stirred for 1 h at 0° C., then treated with benzyl bromide (52.0 μL, 0.440 mmol). The reaction mixture was stirred for 16 h. Water (5 mL) was added and the product was extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine, dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) (5-50% EtOAc/hexanes) to provide the titled compound (100 mg, 75%). MS (ESI/CI): mass calcd. for C19H21ClN2O3, 360.1; m/z found, 361.1 [M+H]+

Workup

stirringThe reaction mixture was stirred for 16 h
extractionthe product was extracted with EtOAc (3×20 mL)
washThe combined organic layers were washed with brine
customdried
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified (FCC) (5-50% EtOAc/hexanes)

Sources & evidence

ORD record: ord-802830f186e64b56a4ac4de6272c9563
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08759345B2

Reaction notes

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