Toluene → 5-Bromo-2-(2-fluoropyridin-4-yl)benzonitrile

HRID 592235Notes

Reaction equation

HRID 592235 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5](I)=[C:6]([CH:9]=1)[C:7]#[N:8].[F:11][C:12]1[CH:17]=[C:16](B(O)O)[CH:15]=[CH:14][N:13]=1.C([O-])([O-])=O.[Na+].[Na+].C1(C)C=CC=CC=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:16]2[CH:15]=[CH:14][N:13]=[C:12]([F:11])[CH:17]=2)=[C:6]([CH:9]=1)[C:7]#[N:8]

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27833962-Fluoropyridine-4-boronic acidHCID 70208745-Bromo-2-iodobenzonitrile

Product 1

HCID 584476735-Bromo-2-(2-fluoropyridin-4-yl)benzonitrile

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

To a sealed tube were added 5-bromo-2-iodobenzonitrile 206-1 (500 mg, 1.6 mmol), 2-fluoropyridin-4-ylboronic acid 205-4 (229 mg, 1.6 mmol), Pd(PPh3)4 (94 mg, 0.08 mmol), Na2CO3 (516 mg, 4.9 mmol), toluene (2 mL), H2O (2 mL) and ethanol (0.5 mL). The reaction mixture was stirred at 120° C. overnight. After cooling to room temperature, the solvents were evaporated and the residue was redissolved in water (5 ml) and extracted with ethyl acetate (8 mL×3). The combined organic phases were dried over Na2SO4, and concentrated. The residue was purified by silica gel flash chromatography and eluted with 15% ethyl acetate in hexane to give 5-bromo-2-(2-fluoropyridin-4-yl)benzonitrile 206-3. MS m/z 277.1 (M+1).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe solvents were evaporated
  3. dissolutionthe residue was redissolved in water (5 ml)
  4. extractionextracted with ethyl acetate (8 mL×3)
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel flash chromatography
  8. washeluted with 15% ethyl acetate in hexane

Sources & evidence

ORD record
ord-4516f268cc054dbaa06fe9f15595bafd
Source dataset
uspto-grants-2016_01
Patent number
US09238646B2

Reaction notes

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