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4-Fluorophenol → 1-(2-Cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-((4-fluorophenoxy)methyl)pyridin-2(1H)-one

HRID 2203070
Notes
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Reaction equation

HRID 2203070 reaction equation
[CH:1]1([C:4]2[N:8]([CH3:9])[C:7]3[CH:10]=[C:11]([N:14]4[CH:19]=[CH:18][C:17]([CH2:20][OH:21])=[CH:16][C:15]4=[O:22])[CH:12]=[CH:13][C:6]=3[N:5]=2)[CH2:3][CH2:2]1.[F:23][C:24]1[CH:29]=[CH:28][C:27](O)=[CH:26][CH:25]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1COCC1>[CH:1]1([C:4]2[N:8]([CH3:9])[C:7]3[CH:10]=[C:11]([N:14]4[CH:19]=[CH:18][C:17]([CH2:20][O:21][C:27]5[CH:28]=[CH:29][C:24]([F:23])=[CH:25][CH:26]=5)=[CH:16][C:15]4=[O:22])[CH:12]=[CH:13][C:6]=3[N:5]=2)[CH2:2][CH2:3]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 97324-FluorophenolHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 896911261-(2-Cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-(hydroxymethyl)pyridin-2(1H)-one

Product 1

HCID 896912081-(2-Cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-((4-fluorophenoxy)methyl)pyridin-2(1H)-oneYield 20.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-(hydroxymethyl)pyridin-2(1H)-one (150 mg), 4-fluorophenol (114 mg) and tributylphosphine (307 mg) in THF (5 ml) was added 1,1′-(azodicarbonyl)dipiperidine (385 mg), and the mixture was stirred at 60° C. for 4 h. The mixture was concentrated in vacuo, and diluted with DCM. The mixture was washed with water and brine successively, dried over Na2SO4, concentrated in vacuo and purified by column chromatography (MeOH/DCM) to afford the title compound (40 mg) as a white solid.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additiondiluted with DCM
  3. washThe mixture was washed with water and brine successively
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. custompurified by column chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-428adc5c54664d7c8227eaf3c37ceb16
Source dataset
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09365540B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes