Potassium Carbonate → 3-Chloro-5-[(2,6-difluoropyridin-4-yl)oxy]benzonitrile

HRID 1952345Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([OH:10])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[F:17][C:18]1[CH:23]=[C:22](F)[CH:21]=[C:20]([F:25])[N:19]=1>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([O:10][C:22]2[CH:21]=[C:20]([F:25])[N:19]=[C:18]([F:17])[CH:23]=2)[CH:3]=1)[C:8]#[N:9]

Participants

Conditions

Temperature: -50 °C

Procedure

Compound 1-4 (577 mg; 3.76 mmol) and potassium carbonate (779 mg; 5.64 mmol) were added to a solution of 2,4,6 trifluoropyridine (500 mg; 3.76 mmol) in DMF with stirring at −50° C. The reaction mixture was slowly warmed to room temperature and then diluted water and EtOAc, after which the aqueous layer was extracted with EtOAc. The combined organic layers were washed with water (3×), brine (2×), dried over MgSO4, and concentrated to an oil. The crude residue was purified via column chromatography (0-25% EtOAc in hexanes.) to give the title compound. MS M+1=266.9. 1H NMR (CDCl3): 6.32 (m, 2H), 7.30 (m, 1H), 7.36 (m, 1H), 7.56 (m, 1H).

Workup

temperatureThe reaction mixture was slowly warmed to room temperature
extractiondiluted water and EtOAc, after which the aqueous layer was extracted with EtOAc
washThe combined organic layers were washed with water (3×), brine (2×)
dry with materialdried over MgSO4
concentrationconcentrated to an oil
customThe crude residue was purified via column chromatography (0-25% EtOAc in hexanes.)

Sources & evidence

ORD record: ord-afdcae7434d24d3f8ce9031849aa040f
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08404856B2

Reaction notes

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