Toluene → 3-(5-Ethyl-6-methoxy-2,4-dimethylpyridin-3-yl)benzonitrile

HRID 1921337Notes

Reaction equation

HRID 1921337 reaction equation
Br[C:2]1[C:3]([CH3:13])=[C:4]([CH2:11][CH3:12])[C:5]([O:9][CH3:10])=[N:6][C:7]=1[CH3:8].[C:14]([C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[CH:20][CH:21]=1)#[N:15].C(=O)([O-])[O-].[Na+].[Na+].C1(C)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.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd].CO>[CH2:11]([C:4]1[C:3]([CH3:13])=[C:2]([C:20]2[CH:21]=[C:16]([CH:17]=[CH:18][CH:19]=2)[C:14]#[N:15])[C:7]([CH3:8])=[N:6][C:5]=1[O:9][CH3:10])[CH3:12]

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27343253-Cyanophenylboronic acidHCID 674921695-Bromo-3-ethyl-2-methoxy-4,6-dimethylpyridine

Product 1

HCID 674922613-(5-Ethyl-6-methoxy-2,4-dimethylpyridin-3-yl)benzonitrileYield 14%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of 5-bromo-3-ethyl-2-methoxy-4,6-dimethylpyridine (254 mg, 1.75 mmol), 3-cyanophenylboronic acid (254 mg, 1.75 mmol), palladium tetrakis(triphenylphosphine) (81.2 mg, 0.07 mmol), 2M aq sodium carbonate (1.15 mL), toluene (10 mL) and methanol (0.7 mL) is reacted following the procedures of Step 4, Example 5. The crude product is purified by HPLC in two runs eluting with a gradient of acetonitrile-20 to 5% water ramping @ 0.5% per min. Product containing fractions from both runs are combined and concentrated to afford 3-(5-ethyl-6-methoxy-2,4-dimethylpyridin-3-yl)benzonitrile (44 mg, 14%) as an oil. LC/MS: MS m/e=267 (M+H); RT 4.41 min.

Workup

  1. customis reacted
  2. customThe crude product is purified by HPLC in two runs
  3. washeluting with a gradient of acetonitrile-20 to 5% water ramping @ 0.5% per min
  4. additionProduct containing fractions from both runs
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-fd0425637d6a4811b1ed1d9d2eb15a7e
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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