Tributylphosphine → 4-((4-Chloro-3-fluorobenzyl)oxy)-1-(2-ethyl-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one

HRID 2203057Notes

Reaction equation

[CH2:1]([C:3]1[N:7]([CH3:8])[C:6]2[CH:9]=[C:10]([N:13]3[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][C:14]3=[O:20])[CH:11]=[CH:12][C:5]=2[N:4]=1)[CH3:2].[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([CH2:28]O)=[CH:24][C:23]=1[F:30].C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1COCC1.O>[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([CH2:28][O:19][C:16]2[CH:17]=[CH:18][N:13]([C:10]3[CH:11]=[CH:12][C:5]4[N:4]=[C:3]([CH2:1][CH3:2])[N:7]([CH3:8])[C:6]=4[CH:9]=3)[C:14](=[O:20])[CH:15]=2)=[CH:24][C:23]=1[F:30]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 1-(2-ethyl-1-methyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one (500 mg), (4-chloro-3-fluorophenyl)methanol (596 mg) and tributylphosphine (1.13 g) in THF (20 ml) was added 1,1′-(azodicarbonyl)dipiperidine (1.41 g), and the reaction mixture was stirred at 60° C. for 2 h. The reaction mixture was cooled to room temperature. The mixture was poured into water and extracted with EtOAc. The extract was washed with brine, dried over MgSO4, concentrated and purified by NH silica gel column chromatography (hexane/EtOAc then EtOAc/MeOH). The resulting solid was recrystallized from EtOH-water to give the title compound (265 mg) as a white solid.

Workup

temperatureThe reaction mixture was cooled to room temperature
extractionextracted with EtOAc
washThe extract was washed with brine
dry with materialdried over MgSO4
concentrationconcentrated
custompurified by NH silica gel column chromatography (hexane/EtOAc
customThe resulting solid was recrystallized from EtOH-water

Sources & evidence

ORD record: ord-2e36b13a73904a7494a89b04c4889022
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365540B2

Reaction notes

Loading…