Toluene → 3-(6-Methoxy-2-methylpyridin-3-yl)benzonitrile

HRID 1921324Notes

Reaction equation

HRID 1921324 reaction equation
[C:1]([C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1)#[N:2].Br[C:13]1[C:14]([CH3:21])=[N:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd].CO>[CH3:20][O:19][C:16]1[N:15]=[C:14]([CH3:21])[C:13]([C:5]2[CH:4]=[C:3]([CH:8]=[CH:7][CH:6]=2)[C:1]#[N:2])=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27343253-Cyanophenylboronic acidHCID 107981463-Bromo-6-methoxy-2-methylpyridine

Product 1

HCID 674923163-(6-Methoxy-2-methylpyridin-3-yl)benzonitrileYield 61%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 887MethanolSolvent

Procedure

To a nitrogen flushed mixture of 3-cyanophenylboronic acid (5.0 g, 34 mmol), 3-bromo-6-methoxy-2-methylpyridine (4.6 g, 22.7 mmol) and palladium tetrakis(triphenylphosphine) (789 mg, 0.68 mmol) is added toluene (150 mL), methanol (12 mL) and sodium carbonate (22.7 mmol) and the mixture is heated overnight at reflux. The cooled reaction is concentrated and the residue is purified by chromatography eluting with cyclohexane-3.2 to 9% ethyl acetate. Product containing fractions are combined and concentrated to afford 3-(6-methoxy-2-methylpyridin-3-yl)benzonitrile (3.09 g, 61% yield) as a white solid. LC/MS: MS m/e=225 (M+H); RT 3.58 min; 1H NMR (CDCl3, δ ppm) 7.65 (1H, m), 7.60 (1H, m), 7.56 (2H, m), 7.40 (1H, d), 6.63 (1H, d), 3.98 (3H, s), 2.40 (3H, s).

Workup

  1. customTo a nitrogen flushed
  2. temperaturethe mixture is heated overnight
  3. temperatureat reflux
  4. customThe cooled reaction
  5. concentrationis concentrated
  6. customthe residue is purified by chromatography
  7. washeluting with cyclohexane-3.2 to 9% ethyl acetate
  8. additionProduct containing fractions
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-53f2c18e32ef496485cad58d7c578025
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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