Phenol → 2-Chloro-6-phenoxy-4-(4-phenoxyphenyl)nicotinonitrile

HRID 81023Notes

Reaction equation

HRID 81023 reaction equation
[Cl:1][C:2]1[N:9]=[C:8](Cl)[CH:7]=[C:6]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)[C:3]=1[C:4]#[N:5].[C:24]1([OH:30])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.C(OCC)(=O)C>[Cl:1][C:2]1[N:9]=[C:8]([O:30][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:7]=[C:6]([C:11]2[CH:12]=[CH:13][C:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:15][CH:16]=2)[C:3]=1[C:4]#[N:5]

Participants

6

Reactant 3

HCID 996PhenolHCID 10796Cesium carbonateHCID 866656822,6-Dichloro-4-(4-phenoxyphenyl)nicotinonitrile

Product 1

HCID 866656842-Chloro-6-phenoxy-4-(4-phenoxyphenyl)nicotinonitrileYield 101%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2,6-dichloro-4-(4-phenoxyphenyl)nicotinonitrile (51 mg, 0.149 mmol, from Step 2 of Example 8), phenol (15.47 mg, 0.164 mmol) and cesium carbonate (97 mg, 0.299 mmol) in DMSO (1.5 mL) was stirred at room temperature for 15 h. The mixture was diluted with ethyl acetate (60 mL), washed with water (2×5 mL), brine (5 mL), dried (MgSO4) and concentrated. Silica gel chromatography, eluting with 0% to 20% ethyl acetate in hexanes, gave 2-chloro-6-phenoxy-4-(4-phenoxyphenyl)nicotinonitrile as a white solid (60 mg, 75% yield). 1H NMR (500 MHz, CDCl3) δ ppm 7.52-7.73 (2H, m), 7.37-7.52 (4H, m), 7.25-7.36 (1H, m), 7.20-7.24 (1H, m), 7.08-7.18 (4H, m), 6.87 (1H, s); MS (ES+) m/z: 399 (M+H); LC retention time: 4.283 min (analytical HPLC Method A).

Workup

  1. washwashed with water (2×5 mL), brine (5 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. washSilica gel chromatography, eluting with 0% to 20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-e14ae2925781465bbf3b100ee2e37a9e
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

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