Sodium Carbonate → 4-[2-(2-Hydroxyethyl)-1-benzofuran-5-yl]benzonitrile

HRID 2416141Notes

Reaction equation

HRID 2416141 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([CH2:10][CH2:11][OH:12])=[CH:7][C:6]=2[CH:13]=1.[C:14]([C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1)#[N:15].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C(OCC)(=O)C.[Pd].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.O>[OH:12][CH2:11][CH2:10][C:8]1[O:9][C:5]2[CH:4]=[CH:3][C:2]([C:19]3[CH:20]=[CH:21][C:16]([C:14]#[N:15])=[CH:17][CH:18]=3)=[CH:13][C:6]=2[CH:7]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 27343264-Cyanophenylboronic acidHCID 222746572-(5-Bromo-1-benzofuran-2-yl)ethan-1-ol

Product 1

HCID 114824394-[2-(2-Hydroxyethyl)-1-benzofuran-5-yl]benzonitrileYield 75%

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

The product from Example 4A (241 mg, 1.0 mmol), 4-cyanophenylboronic acid (221 mg, 1.5 mmol), tetrakis(triphenylphosphine) palladium (0) (57.5 mg, 0.05 mmol), 2-(dicyclohexyl phosphino)biphenyl (35.0 mg, 0.10 mmol), and sodium carbonate (160 mg, 1.5 mmol) were combined in 1,2-dimethoxyethane (16 mL) and water (6 mL) and heated at 80° C. overnight. The mixture was allowed to cool to room temperature and diluted with ethyl acetate (30 mL). The mixture was washed with 5% NaHCO3, 25% brine, dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated to dryness. The residue was purified by silica gel column chromatography to provide 197 mg (75%) of the title compound. An analytical sample was crystallized from diethyl ether; mp; MS-DCl-NH3: 281 (M+NH4)+; 1H-NMR (CDCl3) δ 7.68 (5H, m), 7.51 (1H, d, J=8.5Hz), 7.44 (1H, dd, J=8.5, 1.9 Hz), 6.57 (1H, s), 4.02 (2H, q, J=5.8 Hz), 3.07 (2H, t, J=5.8Hz) 1.70 (1H, t, J=5.8Hz), 13C-NMR (CDCl3) δ 156.9, 154.6, 145.8, 133.9, 132.2, 129.3, 127.6, 122.8, 119.0, 118.8, 111.2, 110.2, 103.7, 60.7, 32.3.

Workup

  1. washThe mixture was washed with 5% NaHCO3, 25% brine
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated to dryness
  5. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3294a73aeea24c08838a464af275e55e
Source dataset
uspto-grants-2004_11
Patent number
US06822101B2

Reaction notes

Loading…