Hexane → [7-(1-Ethylpropyl)-1-methyl-1H-benzimidazol-2-yl](mesityl)methanol

HRID 1665231Notes

Reaction equation

HRID 1665231 reaction equation
C([Li])CCC.CCCCCC.Br[C:13]1[N:17]([CH3:18])[C:16]2[C:19]([CH:23]([CH2:26][CH3:27])[CH2:24][CH3:25])=[CH:20][CH:21]=[CH:22][C:15]=2[N:14]=1.[C:28]1([CH3:38])[CH:33]=[C:32]([CH3:34])[CH:31]=[C:30]([CH3:35])[C:29]=1[CH:36]=[O:37]>C(OCC)C>[CH2:24]([CH:23]([C:19]1[C:16]2[N:17]([CH3:18])[C:13]([CH:36]([C:29]3[C:28]([CH3:38])=[CH:33][C:32]([CH3:34])=[CH:31][C:30]=3[CH3:35])[OH:37])=[N:14][C:15]=2[CH:22]=[CH:21][CH:20]=1)[CH2:26][CH3:27])[CH3:25]

Participants

6

Reactant 4

HCID 8058HexaneHCID 102542,4,6-TrimethylbenzaldehydeHCID 592020912-Bromo-7-(1-ethylpropyl)-1-methyl-1H-benzimidazoleHCID 178418339Butyllithium

Product 1

HCID 59202084[7-(1-Ethylpropyl)-1-methyl-1H-benzimidazol-2-yl](mesityl)methanolYield 16%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

A solution of n-butyllithium in n-hexane (1.6M solution, 0.25 mL, 0.40 mmol) was added dropwise to a solution of 2-bromo-7-(1-ethylpropyl)-1-methyl-1H-benzimidazole (100 mg, 0.36 mmol) in diethyl ether (4 mL) at 0° C. To the reaction mixture was added a solution of mesitaldehyde (74 mg, 0.50 mmol) in diethyl ether (1 mL) at 0° C. The reaction mixture was stirred for 0.5 hr, and the reaction was quenched by the addition of 1N hydrochloric acid to the mixture, and the mixture was extracted with ethyl acetate. The organics were dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by preparative HPLC eluting with a 10-100% water/acetonitrile gradient mixture containing 0.1% trifluoroacetic acid. The fractions containing the title compound were concentrated in vacuo, and the residue was diluted with ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate solution. The organics were dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The resulting solid was recrystallized from ethanol/water to give the title compound (20 mg, 0.057 mmol, 16%) as colorless crystals.

Workup

  1. customthe reaction was quenched by the addition of 1N hydrochloric acid to the mixture
  2. extractionthe mixture was extracted with ethyl acetate
  3. dry with materialThe organics were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative HPLC
  7. washeluting with a 10-100% water/acetonitrile gradient mixture
  8. additioncontaining 0.1% trifluoroacetic acid
  9. additionThe fractions containing the title compound
  10. concentrationwere concentrated in vacuo
  11. additionthe residue was diluted with ethyl acetate
  12. washwashed with saturated aqueous sodium hydrogen carbonate solution
  13. dry with materialThe organics were dried over anhydrous magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customThe resulting solid was recrystallized from ethanol/water

Sources & evidence

ORD record
ord-f3abd8fcca8740df9990203611733d6c
Source dataset
uspto-grants-2011_10
Patent number
US08039500B2

Reaction notes

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