Sodium hydride → 3-[4-(benzyloxy)phenyl]-1-(difluoromethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

HRID 82597Notes

Reaction equation

HRID 82597 reaction equation
[Na+].[F:2][C:3]([F:8])(Cl)C([O-])=O.[CH2:9]([O:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]2[C:27]3=[N:28][CH:29]=[CH:30][CH:31]=[C:26]3[NH:25][C:24]2=[O:32])=[CH:19][CH:18]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[Br-].[Li+].[H-].[Na+].[Cl-].[Cl-].[Ca+2]>CN(C=O)C.CO>[CH2:9]([O:16][C:17]1[CH:18]=[CH:19][C:20]([N:23]2[C:27]3=[N:28][CH:29]=[CH:30][CH:31]=[C:26]3[N:25]([CH:3]([F:8])[F:2])[C:24]2=[O:32])=[CH:21][CH:22]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

8

Reactant 5

HCID 24758Sodium hydrideHCID 82050Lithium BromideHCID 2734985Sodium chlorodifluoroacetateHCID 5284359Calcium ChlorideHCID 585776613-[4-(benzyloxy)phenyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

Product 1

HCID 585772453-[4-(benzyloxy)phenyl]-1-(difluoromethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-oneYield 18.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

Difluorochloroacetic acid sodium salt (1.922 g) was added to a solution of 3-[4-(benzyloxy)phenyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (2 g), lithium bromide (1.095 g) and NaH (0.290 g) in DMF(20 ml) at 0° C. The mixture was stirred at 140° C. under a dry atmosphere (CaCl2 tube) for 1 h. The reaction mixture was diluted with MeOH and concentrated in vacuo. The residue was purified by column chromatography (NH silica gel, eluted with 0%-30% EtOAc in hexane) to give 3-[4-(benzyloxy)phenyl]-1-(difluoromethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (420 mg) as a white solid.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by column chromatography (NH silica gel, eluted with 0%-30% EtOAc in hexane)

Sources & evidence

ORD record
ord-ef9cebe7cb0f41bab20bc5a063de4f3d
Source dataset
uspto-grants-2014_09
Patent number
US08846713B2

Reaction notes

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