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

HRID 2404420Notes

Reaction equation

HRID 2404420 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.[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 930741-Methyl-3-pyrrolidinolHCID 5360545Sodium

Product 1

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

Reagents, catalysts & solvents 1

HCID 6395Methanesulfonic AcidSolvent

Procedure

272A 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, poored into water which is then made alkaline with concentrated sodium hydroxyde 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-8cc0374cc61b47659e56209bff23085c
Source dataset
uspto-grants-2014_08
Patent number
US08802664B2

Reaction notes

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