Water → 2-[(1-methylpyrrolidin-3-yloxy)phenyl-methyl]-1H-benzimidazole

HRID 572832Notes

Reaction equation

HRID 572832 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]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[OH:11].[CH3:18][N:19]1[CH2:23][CH2:22][CH:21](O)[CH2:20]1.O.[OH-].[Na+]>CS(O)(=O)=O>[CH3:18][N:19]1[CH2:23][CH2:22][CH:21]([O:11][CH:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:2]2[NH:3][C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[N:1]=2)[CH2:20]1

Participants

6

Reactant 4

HCID 962WaterHCID 57922-(alpha-Hydroxybenzyl)benzimidazoleHCID 14798Sodium HydroxideHCID 930741-Methyl-3-pyrrolidinol

Product 1

HCID 668358672-[(1-methylpyrrolidin-3-yloxy)phenyl-methyl]-1H-benzimidazole

Reagents, catalysts & solvents 1

HCID 6395Methanesulfonic AcidSolvent

Procedure

A mixture of (1H-benzimidazol-2-yl)phenylmethanol (611 mg) and 1-methyl-3-pyrrolidinol (263 mg) in methanesulfonic acid (1.3 mL) is heated for 4 hours in a sealed tube at a temperature close to 140° C. The mixture is cooled back to room temperature, poured into water which is then made alkaline with concentrated sodium hydroxide solution. The aqueous phase is extracted with ethyl acetate. Pooled extracts are dried over magnesium sulfate, 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 2-[(1-methylpyrrolidin-3-yloxy)phenyl-methyl]-1H-benzimidazole melting at 53° C.

Workup

  1. temperatureis heated for 4 hours in a sealed tube at a temperature
  2. customclose to 140° C
  3. extractionThe aqueous phase is extracted with ethyl acetate
  4. dry with materialPooled extracts are dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is purified by column chromatography over silica gel (gradient dichloromethane/methanol from 100/0 to 90/10)

Sources & evidence

ORD record
ord-dc692da432f04e48b33a298f6f060cd7
Source dataset
uspto-grants-2015_05
Patent number
US09029357B2

Reaction notes

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