1H-Isoindole-1,3(2H)-dione, 2-(2-bromoethyl)- → tert-butyl 3-(1-(2-(1,3-dioxoisoindolin-2-yl)ethyl)-1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate

HRID 1096661Notes

Reaction equation

HRID 1096661 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH: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][N:28]1[C:36](=[O:37])[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29]1=[O:38]>CN(C=O)C>[O:38]=[C:29]1[C:30]2[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:36](=[O:37])[N:28]1[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[CH: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 113251H-Isoindole-1,3(2H)-dione, 2-(2-bromoethyl)-HCID 24758Sodium hydrideHCID 532170522-(N-Boc-piperidin-3-yl)-1H-benzoimidazole

Product 1

HCID 66786754tert-butyl 3-(1-(2-(1,3-dioxoisoindolin-2-yl)ethyl)-1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Tert-butyl 3-(1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate (4.36 mmol, 1.3 g) was added to a 50 mL oven-dried round-bottomed flask equipped for stirring under nitrogen. DMF (15 mL) was added and the solution was cooled to 0° C. NaH (4.80 mmol, 192 mg) was then added in one portion and the resultant solution was stirred at 0° C. for 0.5 hr. At this time 2-(2-bromoethyl)isoindoline-1,3-dione (5.01 mmoles, 1.27 g) was added; the ice bath was removed and the reaction solution was allowed to warm to room temperature and stirred for 16 hrs. The reaction was then heated to 100° C. and allowed to stir for an additional 16 hrs. Analysis of the reaction solution by LC/MS indicated about an approx. 10% conversion to the desired title compound (129A). The reaction was cooled to rt and 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 tert-butyl 3-(1-(2-(1,3-dioxoisoindolin-2-yl)ethyl)-1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate (129A) as a mixture of products that was carried onto the next step without further purification. ESI-MS: m/z 475.3 (M+H)+.

Workup

  1. customequipped
  2. customthe ice bath was removed
  3. temperatureto warm to room temperature
  4. stirringstirred for 16 hrs
  5. temperatureThe reaction was then heated to 100° C.
  6. stirringto stir for an additional 16 hrs
  7. temperatureThe reaction was cooled to rt
  8. additionpoured into ice-water
  9. extractionextracted with ethyl acetate
  10. washwashed once with saturated aqueous sodium chloride
  11. customThe organic layer was collected
  12. dry with materialsubsequently dried with anhydrous Na2SO4
  13. filtrationfiltered
  14. customThis filtrate was collected
  15. concentrationconcentrated
  16. customdried in-vacuo

Sources & evidence

ORD record
ord-70c0d5e74de146cd9cef11695c3a6bd3
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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