Benzimidazole → HCID 45590701, compound

HRID 1096673Notes

Reaction equation

HRID 1096673 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[H-].[Na+].Br[CH2:13][CH2:14][CH2:15][O:16][CH3:17]>>[CH3:17][O:16][CH2:15][CH2:14][CH2:13][N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1

Participants

4

Reactant 3

HCID 5798BenzimidazoleHCID 24758Sodium hydrideHCID 5245511-Bromo-3-methoxypropane

Product 1

HCID 45590701HCID 45590701, compoundYield 76%

Conditions

Temperature
0 °C

Procedure

1H-benzo[d]imidazole (12.7 mmoles, 1.5 g) was added to an oven dried 200 mL round-bottomed flask equipped for stirring under nitrogen. DMF (20 mL) was added and the solution was cooled to 0° C. with an ice bath. To this cooled solution was added NaH (60% in mineral oil, 13.3 mmoles, 533 mg) in two portions. The resultant solution was allowed to stir at 0° C. for 30 minutes under nitrogen. 1-bromo-3-methoxypropane (14.0 mmoles, 2.14 g) was added and the solution was allowed to warm to room temperature and stirred for 1 hr. The reaction solution was then poured into ice-water, extracted with ethyl acetate, and washed once with saturated aqueous sodium chloride. The organic layer was collected and subsequently dried with anhydrous Na2SO4 and filtered. This filtrate was collected, concentrated, and dried in-vacuo. This material was then purified by chromatography on silica gel (5-15% CH3OH/CH2Cl2) to afford 1-(3-methoxypropyl)-1H-benzo[d]imidazole (137A) as a clear oil (9.62 mmoles, 1.83 g, 76% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.10 (dt, J=12.57, 6.22 Hz, 2H) 3.29 (t, J=5.68 Hz, 2H) 3.34 (s, 3H) 4.31 (t, J=6.69 Hz, 2H) 7.23-7.34 (m, 2H) 7.37-7.45 (m, 1H) 7.78-7.83 (m, 1H) 7.89 (s, 1H). ESI-MS: m/z 191.4 (M+H)+.

Workup

  1. customdried 200 mL round-bottomed flask
  2. customequipped
  3. additionDMF (20 mL) was added
  4. stirringto stir at 0° C. for 30 minutes under nitrogen
  5. temperatureto warm to room temperature
  6. stirringstirred for 1 hr
  7. extractionextracted with ethyl acetate
  8. washwashed once with saturated aqueous sodium chloride
  9. customThe organic layer was collected
  10. dry with materialsubsequently dried with anhydrous Na2SO4
  11. filtrationfiltered
  12. customThis filtrate was collected
  13. concentrationconcentrated
  14. customdried in-vacuo
  15. customThis material was then purified by chromatography on silica gel (5-15% CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-0bd8ea04bbbe4bda92e3eecd4be0ff01
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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