Sodium hydride → 1-cyclopropylmethyl-7-methylsulfanyl-1H-benzoimidazole

HRID 657522Notes

Reaction equation

HRID 657522 reaction equation
[CH3:1][S:2][C:3]1[C:11]2[N:10]=[CH:9][NH:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.[H-].[Na+].Br[CH2:15][CH:16]1[CH2:18][CH2:17]1>CN(C=O)C>[CH:16]1([CH2:15][N:8]2[C:7]3[CH:6]=[CH:5][CH:4]=[C:3]([S:2][CH3:1])[C:11]=3[N:10]=[CH:9]2)[CH2:18][CH2:17]1.[CH:16]1([CH2:15][N:10]2[C:11]3[C:3]([S:2][CH3:1])=[CH:4][CH:5]=[CH:6][C:7]=3[N:8]=[CH:9]2)[CH2:18][CH2:17]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 251423217-(Methylthio)-1H-benzo[d]imidazole

Product 2

HCID 594425971-cyclopropylmethyl-7-methylsulfanyl-1H-benzoimidazoleHCID 594426631-cyclopropylmethyl-4-methylsulfanyl-1H-benzoimidazole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

2 g of 4-methylsulfanyl-1H-benzoimidazole were dissolved in 20 ml of dry DMF. 0.6 g of sodium hydride (60% strength in mineral oil) were added portionwise at 0° C. After stirring for 1 h at 20° C., the mixture was cooled to 0° C. and bromomethylcyclopropane (1.5 ml) was added. The reaction mixture was stirred for 18 h at 20° C. The solvent was evaporated in vacuo and the residue was taken up in water and EA (100 ml each). The phases were separated, the aqueous phase was extracted with EA, and the combined organic phases were washed with brine and dried over sodium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography (100 g silica gel; DCM/EA, gradient from 100:0 to 80:20) to yield 1.2 g of 1-cyclopropylmethyl-4-methylsulfanyl-1H-benzoimidazole and 0.8 g of 1-cyclopropylmethyl-7-methylsulfanyl-1H-benzoimidazole.

Workup

  1. temperaturethe mixture was cooled to 0° C.
  2. stirringThe reaction mixture was stirred for 18 h at 20° C
  3. customThe solvent was evaporated in vacuo
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted with EA
  6. washthe combined organic phases were washed with brine
  7. dry with materialdried over sodium sulfate
  8. customThe solvent was removed in vacuo
  9. customThe crude product was purified by flash chromatography (100 g silica gel; DCM/EA, gradient from 100:0 to 80:20)

Sources & evidence

ORD record
ord-b308309d1f014e869475e090f6ca6bf8
Source dataset
uspto-grants-2011_12
Patent number
US08076324B2

Reaction notes

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