Ethanol → 2-Fluoro-3-(4-methylpyridin-3-yl)benzonitrile

HRID 593742Notes

Reaction equation

HRID 593742 reaction equation
Br[C:2]1[C:3]([F:10])=[C:4]([CH:7]=[CH:8][CH:9]=1)[C:5]#[N:6].CC1(C)C(C)(C)OB([C:19]2[C:28]3[C:23](=CC=C[CH:27]=3)[CH:22]=[N:21][CH:20]=2)O1.C(O)C.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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.O>[F:10][C:3]1[C:2]([C:19]2[CH:20]=[N:21][CH:22]=[CH:23][C:28]=2[CH3:27])=[CH:9][CH:8]=[CH:7][C:4]=1[C:5]#[N:6]

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27605944-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolineHCID 27612003-Bromo-2-fluorobenzonitrile

Product 1

HCID 867303982-Fluoro-3-(4-methylpyridin-3-yl)benzonitrileYield 87%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 3-bromo-2-fluorobenzonitrile (2.0 g, 10.00 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinoline (2.81 g, 11.00 mmol) in a mixture of DME (30 mL), ethanol (15 mL), and water (15 mL) was added Na2CO3 (4.24 g, 40.0 mmol). This suspension was degassed with a stream of N2 for 10 minutes and then tetrakis(triphenylphosphine)palladium(0) (0.578 g, 0.500 mmol) was added followed by degassing with nitrogen for 10 minutes. The tube was then sealed and heated to 90° C. for 14 hours. The vessel was cooled to room temperature and diluted with EtOAc and water. The mixture was further diluted with brine and extracted three times with EtOAc. The combined organics were dried over MgSO4, filtered, and concentrated to give the crude product as a brown oil. The crude material was purified by flash chromatography on silica using an ISCO machine (80 g SiO2 column, 60 mL/min, 0-20% acetone in CH2Cl2 over 20 minutes, tr=8 minutes) to give the title compound (2.18 g, 8.69 mmol, 87% yield) as a pale yellow solid. ESI MS (M+H)+=249.1.

Workup

  1. customThis suspension was degassed with a stream of N2 for 10 minutes
  2. customby degassing with nitrogen for 10 minutes
  3. customThe tube was then sealed
  4. temperatureThe vessel was cooled to room temperature
  5. additiondiluted with EtOAc and water
  6. additionThe mixture was further diluted with brine
  7. extractionextracted three times with EtOAc
  8. dry with materialThe combined organics were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give the crude product as a brown oil
  12. customThe crude material was purified by flash chromatography on silica using an ISCO machine (80 g SiO2 column, 60 mL/min, 0-20% acetone in CH2Cl2 over 20 minutes, tr=8 minutes)

Sources & evidence

ORD record
ord-4fb4f65c58a74d16bac1ecd90da853cf
Source dataset
uspto-grants-2016_01
Patent number
US09242967B2

Reaction notes

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