Water → 2-(4-(Trifluoromethyl)phenyl)isonicotinonitrile

HRID 1479801Notes

Reaction equation

HRID 1479801 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=[CH:4][N:3]=1.O.C(=O)(O)[O-].[Na+].[F:16][C:17]([F:28])([F:27])[C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1>C(COC)OC>[F:16][C:17]([F:28])([F:27])[C:18]1[CH:23]=[CH:22][C:21]([C:2]2[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=[CH:4][N:3]=2)=[CH:20][CH:19]=1

Participants

6

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 5686382-Chloro-4-cyanopyridineHCID 27343894-(Trifluoromethyl)phenylboronic acid

Product 1

HCID 668323802-(4-(Trifluoromethyl)phenyl)isonicotinonitrileYield 47%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

2-Chloropyridine-4-carbonitrile 19 (2.96 g, 21.35 mmol) was dissolved in 100 ml of dimethoxyethane. The solution was added with 70 ml of water, sodium bicarbonate (3 equiv., 5.38 g), [4-(trifluoromethyl)phenyl]boronic acid (1.2 equiv., 4.87 g) and the mixture was then stirred at rt for 5′. The mixture was degassed and placed under argon. A catalytic amount of tetrakispalladium was added and the mixture heated at 100° C. overnight. The solvents were evaporated off and the resulting residue dissolved with ethyl acetate and then washed with water and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The crude was crystallized from ethyl acetate and petroleum ether to give a beige solid. (2.5 g, 47% yield).

Workup

  1. customThe mixture was degassed
  2. additionA catalytic amount of tetrakispalladium was added
  3. temperaturethe mixture heated at 100° C. overnight
  4. customThe solvents were evaporated off
  5. dissolutionthe resulting residue dissolved with ethyl acetate
  6. washwashed with water and brine
  7. dry with materialThe organic phase was dried over sodium sulfate
  8. concentrationconcentrated under vacuum
  9. customThe crude was crystallized from ethyl acetate and petroleum ether
  10. customto give a beige solid

Sources & evidence

ORD record
ord-7314503ba45f4ebd92f8ab57aab93ecc
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Reaction notes

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