Sodium hydride → (R)-tert-butyl 3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate

HRID 1096597Notes

Reaction equation

HRID 1096597 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C@@H:10]1[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]1.[H-].[Na+].Br[CH2:26][CH2:27][CH2:28][O:29][CH3:30]>CN(C=O)C>[CH3:30][O:29][CH2:28][CH2:27][CH2:26][N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C@@H:10]1[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 5245511-Bromo-3-methoxypropaneHCID 66791508(R)-tert-Butyl 3-(1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate

Product 1

HCID 66786343(R)-tert-butyl 3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylateYield 96.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(R)-tert-Butyl 3-(1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate (7B) (9.95 mmol, 3.0 g) was added to a 200 mL round-bottomed flask equipped for stirring under nitrogen. DMF (50 mL) was added and the resultant solution was cooled to 0° C. with an ice bath. NaH (60% in mineral oil, 11.95 mmol, 0.478 g) was then added and the subsequent solution was allowed to stir under nitrogen for 0.5 hr. At this time 1-bromo-3-methoxypropane (12.44 mmol, 1.90 g) was added, the ice bath was removed and the reaction solution was allowed to warm to room temperature and stir fort 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 affording a brown oil. This material was then purified by chromatography on silica gel (3-10% CH3OH in CH2Cl2) to afford (R)-tert-butyl 3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate (7C) as a brown oil (9.63 mmol, 3.6 g, 96% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.55-1.71 (br.s., 1H) 1.79-1.88 (br.s., 1H) 2.04-2.13 (m, 4H) 2.74-2.88 (br.s., 1H) 2.98-3.38 (m, 7H) 4.21-4.39 (m, 3H) 7.22-7.28 (m, 2H) 7.34-7.40 (dd, 1H, 6.57 Hz, 2.02 Hz) 7.72-7.77 (dd, 1H, 6.57 Hz, 2.02 Hz). ESI-MS: m/z 374.4 (M+H)+.

Workup

  1. customequipped
  2. stirringto stir under nitrogen for 0.5 hr
  3. customthe ice bath was removed
  4. stirringstir fort hr
  5. additionThe reaction solution was then poured into ice-water
  6. extractionextracted with ethyl acetate
  7. washwashed once with saturated aqueous sodium chloride
  8. customThe organic layer was collected
  9. dry with materialsubsequently dried with anhydrous Na2SO4
  10. filtrationfiltered
  11. customThis filtrate was collected
  12. concentrationconcentrated
  13. customdried in-vacuo
  14. customaffording a brown oil
  15. customThis material was then purified by chromatography on silica gel (3-10% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-ffd3700e2bd54a71855dba971a84a199
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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