Pyridine → 3-Chloro-5-(4-(4-methoxyphenoxy)phenyl)isonicotinonitrile

HRID 81029Notes

Reaction equation

HRID 81029 reaction equation
[Cl:1][C:2]1[CH:9]=[N:8][CH:7]=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)[C:3]=1[C:4]#[N:5].[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1.N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:9]=[N:8][CH:7]=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([O:16][C:22]3[CH:23]=[CH:24][C:19]([O:18][CH3:17])=[CH:20][CH:21]=3)=[CH:12][CH:11]=2)[C:3]=1[C:4]#[N:5]

Participants

6

Reactant 3

HCID 1049PyridineHCID 201262(4-Methoxyphenyl)boronic acidHCID 669269303-Chloro-5-(4-hydroxyphenyl)isonicotinonitrile

Product 1

HCID 669270193-Chloro-5-(4-(4-methoxyphenoxy)phenyl)isonicotinonitrileYield 68%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-chloro-5-(4-hydroxyphenyl)isonicotinonitrile (50 mg, 0.217 mmol), 4-methoxyphenylboronic acid (132 mg, 0.867 mmol), copper(II) acetate (47.2 mg, 0.260 mmol), pyridine (0.140 mL, 1.734 mmol) and 4 A molecular sieves (300 mg) in dichloromethane (6 mL) was stirred under air at room temperature for 4 days. The mixture was filtered through a CELITE® pad to remove molecular sieves (rinsed with dichloromethane), quenched with saturated ammonium chloride (20 mL) and ammonium hydroxide (2 mL) and extracted with dichloromethane (3×10 mL). The combined extracts were dried (MgSO4) and concentrated. Silica gel chromatography, loading with toluene and eluting with 5-30% ethyl acetate in hexanes, gave 3-chloro-5-(4-(4-methoxyphenoxy)phenyl)isonicotinonitrile as a white solid (49.7 mg, 67% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.72 (1H, s), 8.68 (1H, s), 7.45-7.59 (2H, m), 6.99-7.14 (4H, m), 6.88-6.99 (2H, m), 3.83 (3H, s); MS (ES+) m/z: 337 (M+H); LC retention time: 4.321 min (analytical HPLC Method A).

Workup

  1. filtrationThe mixture was filtered through a CELITE® pad
  2. customto remove molecular
  3. washsieves (rinsed with dichloromethane)
  4. customquenched with saturated ammonium chloride (20 mL) and ammonium hydroxide (2 mL)
  5. extractionextracted with dichloromethane (3×10 mL)
  6. dry with materialThe combined extracts were dried (MgSO4)
  7. concentrationconcentrated
  8. washeluting with 5-30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-ef3a252ebd414583ab9533d070182cc7
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

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