Benzaldehyde → 2-(alpha-Hydroxybenzyl)benzimidazole

HRID 572833Notes

Reaction equation

HRID 572833 reaction equation
N1(C[N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[CH:8]2)CCCC1.C([Li])CCC.[CH:21](=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>O1CCCC1>[NH:9]1[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[N:7]=[C:8]1[CH:21]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[OH:28]

Participants

5

Reactant 3

HCID 240BenzaldehydeHCID 2090961-(Pyrrolidin-1-ylmethyl)benzimidazoleHCID 178418339Butyllithium

Product 1

HCID 57922-(alpha-Hydroxybenzyl)benzimidazole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-pyrrolidin-1-ylmethyl-1H-benzimidazole (5 g) in tetrahydrofurane (20 mL) cooled at a temperature close to −80° C., is added a 2.5M solution of butyl lithium in hexanes (10 mL). The mixture is stirred for 15 minutes. A solution of benzaldehyde (2.64 g) in tetrahydrofurane (20 mL) is added. The mixture is stirred at a temperature close to −80° C. for 1 hour, then at a temperature close to −20° C. for 2 hours. The reaction is quenched by addition of saturated ammonium chloride. The mixture is extracted with ethyl acetate. Pooled extracts are washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by column chromatography over silica gel (gradient dichloromethane/methanol from 100/0 to 90/10) to give (1H-benzimidazol-2-yl)phenylmethanol used without further purification.

Workup

  1. customclose to −80° C.
  2. stirringThe mixture is stirred at a temperature
  3. customclose to −80° C. for 1 hour
  4. customat a temperature close to −20° C. for 2 hours
  5. customThe reaction is quenched by addition of saturated ammonium chloride
  6. extractionThe mixture is extracted with ethyl acetate
  7. washPooled extracts are washed with brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue is purified by column chromatography over silica gel (gradient dichloromethane/methanol from 100/0 to 90/10)

Sources & evidence

ORD record
ord-129a9b29fd6e409d9a5a6eeac379f777
Source dataset
uspto-grants-2015_05
Patent number
US09029357B2

Reaction notes

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