Tetrahydrofuran → 5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole-2-carbaldehyde

HRID 1627312Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C:9]([C:12]2[N:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[CH:15]=[N:14][CH:13]=2)([CH3:11])[CH3:10])[CH:5]=[CH:6][C:7]=1[Cl:8].C1C[O:27][CH2:26]C1.[Li]CCCC>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]([C:12]2[N:16]([C:17]3[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=3)[C:15]([CH:26]=[O:27])=[N:14][CH:13]=2)([CH3:11])[CH3:10])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole (770 mg, 2.2 mmol) in anhyd THF (10 mL) at −78° C. was added n-BuLi (1.4 mL, 2.0M in hexane, 2.8 mmol) dropwise. After stirring 1 h at −78° C., anhyd DMF (0.85 mL) was added in one portion. After stirring another 3 h at −78° C., the reaction was quenched with water. After warming to ambient temperature, the mixture was extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4, and concentrated in vacuo. The crude material was purified by column chromatography (silica, 0-90% EtOAc/Hex) to give 5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole-2-carbaldehyde as a white solid (740 mg, 89% yield).

Workup

stirringAfter stirring another 3 h at −78° C.
customthe reaction was quenched with water
temperatureAfter warming to ambient temperature
extractionthe mixture was extracted with EtOAc
washThe combined extracts were washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customThe crude material was purified by column chromatography (silica, 0-90% EtOAc/Hex)

Sources & evidence

ORD record: ord-7ae0f66321074ff8a568b5346cfcbc7e
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785488B2

Reaction notes

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