Potassium Fluoride → 3-Fluoro-5-(4-phenoxyphenyl)isonicotinonitrile

HRID 81034Notes

Reaction equation

HRID 81034 reaction equation
Cl[C:2]1[CH:9]=[N:8][CH:7]=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:12][CH:11]=2)[C:3]=1[C:4]#[N:5].[F-:23].[K+]>CS(C)=O.O>[F:23][C:2]1[CH:9]=[N:8][CH:7]=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:12][CH:11]=2)[C:3]=1[C:4]#[N:5]

Participants

5

Reactant 2

HCID 522689Potassium FluorideHCID 669269133-Chloro-5-(4-phenoxyphenyl)isonicotinonitrile

Product 1

HCID 669269833-Fluoro-5-(4-phenoxyphenyl)isonicotinonitrileYield 69%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-chloro-5-(4-phenoxyphenyl)isonicotinonitrile (11.8 g, 38.5 mmol) and potassium fluoride (11.17 g, 192 mmol) in DMSO (500 mL) was heated to 120° C. for 10 days. The mixture was diluted with water (1 L) and extracted with ethyl acetate (3×400 mL). The combined extracts were washed with brine (100 mL), dried (MgSO4) and concentrated. Silica gel chromatography, eluting with 0-15% ethyl acetate in dichloromethane-hexanes (1:2), gave 3-fluoro-5-(4-phenoxyphenyl)isonicotinonitrile as tan solid (7.66 g, 69% yield). 1H NMR (500 MHz, CDCl3) δ ppm 8.67 (1H, s), 8.64 (1H, s), 7.52-7.62 (2H, m), 7.36-7.46 (2H, m), 7.20 (1H, t, J=7.42 Hz), 7.05-7.17 (4H, m); MS (ES+) m/z: 291 (M+H); LC retention time: 4.118 min (analytical HPLC Method A).

Workup

  1. extractionextracted with ethyl acetate (3×400 mL)
  2. washThe combined extracts were washed with brine (100 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. washSilica gel chromatography, eluting with 0-15% ethyl acetate in dichloromethane-hexanes (1:2)

Sources & evidence

ORD record
ord-24f29164e2574d099db48fdea1f25307
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

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