Dimethylformamide → 6-Methylbenzofuran-2-carbonitrile

HRID 1773214Notes

Reaction equation

HRID 1773214 reaction equation
Br[C:2](Br)=[CH:3][C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][C:5]=1[OH:11].C([O-])([O-])=O.[Na+].[Na+].[CH3:19][N:20](C=O)C>[Cu]I.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:10][C:7]1[CH:8]=[CH:9][C:4]2[CH:3]=[C:2]([C:19]#[N:20])[O:11][C:5]=2[CH:6]=1

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 1184526172-(2,2-Dibromovinyl)-5-methylphenol

Product 1

HCID 289100396-Methylbenzofuran-2-carbonitrile

Reagents, catalysts & solvents 3

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
80 °C

Procedure

To a 500 mL 3-neck flask was added 2-(2,2-dibromovinyl)-5-methylphenol (17.7 g, 60.6 mmol), CuI (1.16 g, 6.06 mmol), Na2CO3 (12.85 g, 121 mmol) and DMF (120 mL). The reaction was heated to 80° C. for 6 hr. After 6 hr the r×n was cooled to RT and anhydrous K4Fe(CN)6 (4.47 g, 12.12 mmol), Pd(OAc)2 (2.04 g, 3.03 mmol) and PPh3 (0.32 g, 1.21 mmol) were added to the reaction and the reaction was flushed with nitrogen for 10 min. The reaction was then heated to 120° C. for 18 hr. After 18 hr the r×n was cooled to RT and diluted with EtOAc. The reaction mixture was filtered through a silica plug to remove solids and flushed with EtOAc. The collected filtrates were diluted with water and brine and extracted with EtOAc×2. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude mixture was purified via silica gel FCC, 100% Heptane-20% EtOAc/80% Heptane to give a yellow solid, 6-methylbenzofuran-2-carbonitrile (5.1 g). 1H NMR (400 MHz, DMSO-d6) δ 2.47 (s, 3H), 7.27 (ddd, J=8.2, 1.4, 0.7 Hz, 1H), 7.57 (s, 1H), 7.71 (d, J=8.1 Hz, 1H), 8.05 (d, J=1.0 Hz, 1H).

Workup

  1. temperatureAfter 6 hr the r×n was cooled to RT
  2. customthe reaction was flushed with nitrogen for 10 min
  3. temperatureThe reaction was then heated to 120° C. for 18 hr
  4. temperatureAfter 18 hr the r×n was cooled to RT
  5. additiondiluted with EtOAc
  6. filtrationThe reaction mixture was filtered through a silica plug
  7. customto remove solids
  8. customflushed with EtOAc
  9. additionThe collected filtrates were diluted with water and brine
  10. extractionextracted with EtOAc×2
  11. washThe combined organic layers were washed with brine
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customThe crude mixture was purified via silica gel FCC, 100% Heptane-20% EtOAc/80% Heptane

Sources & evidence

ORD record
ord-37df925819094586b0813c89acf91423
Source dataset
uspto-grants-2016_02
Patent number
US09255093B2

Reaction notes

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