4-Bromobutyronitrile → 4-(2-Hydroxymethyl-benzoimidazol-1-yl)-butyronitrile

HRID 1634018Notes

Reaction equation

HRID 1634018 reaction equation
[OH:1][CH2:2][C:3]1[NH:4][C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[H-].[Na+].Br[CH2:15][CH2:16][CH2:17][C:18]#[N:19].CCOC(C)=O.CO>CN(C=O)C.C1COCC1>[OH:1][CH2:2][C:3]1[N:4]([CH2:15][CH2:16][CH2:17][C:18]#[N:19])[C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1

Participants

6

Reactant 4

HCID 214124-BromobutyronitrileHCID 24758Sodium hydrideHCID 785692-(Hydroxymethyl)-1H-benzimidazoleHCID 21584119Ethylacetate methanol

Product 1

HCID 225957974-(2-Hydroxymethyl-benzoimidazol-1-yl)-butyronitrileYield 51.4%

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

To a solution of 2-hydroxymethylbenzimidazole (29.63 g, 200 mmol) in a mixture of DMF/THF (150 mL, 1:1) was added sodium hydride (60% in mineral oil, 8.4 g, 210 mmol) in several portions at room temperature. After stirring for 1 hour, 4-bromobutyronitrile (29.6 g, 200 mmol) was added and the resulting solution was stirred at 80° C. for 16 hours. The solvent was evaporated and the residue diluted with water and extracted with EtOAc. The combined extracts were dried over MgSO4 and evaporated. The residue was purified by flash chromatography (gradient, EtOAc/hexane, 1:1 to 2:1, then EtOAc/MeOH, 10:1) to give 22.11 g (51% yield) 4-(2-hydroxymethyl-benzoimidazol-1-yl)-butyronitrile, 68 as a white solid.

Workup

  1. stirringthe resulting solution was stirred at 80° C. for 16 hours
  2. customThe solvent was evaporated
  3. additionthe residue diluted with water
  4. extractionextracted with EtOAc
  5. dry with materialThe combined extracts were dried over MgSO4
  6. customevaporated
  7. customThe residue was purified by flash chromatography (gradient, EtOAc/hexane, 1:1 to 2:1

Sources & evidence

ORD record
ord-0d34578ac4ad4458be599413d91a07b6
Source dataset
uspto-grants-2003_01
Patent number
US06506738B1

Reaction notes

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