6-(5-Bromo-furan-2-yl)-nicotinonitrile → 6-[5-(4-Cyanobenzyl)furan-2-yl]nicotinonitrile

HRID 853810Notes

Reaction equation

HRID 853810 reaction equation
Br[C:2]1[O:6][C:5]([C:7]2[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][N:8]=2)=[CH:4][CH:3]=1.[Br-].[C:16]([C:18]1[CH:25]=[CH:24][C:21]([CH2:22][Zn+])=[CH:20][CH:19]=1)#[N:17]>O1CCCC1.ClCCl.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.[Pd]>[C:16]([C:18]1[CH:25]=[CH:24][C:21]([CH2:22][C:2]2[O:6][C:5]([C:7]3[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][N:8]=3)=[CH:4][CH:3]=2)=[CH:20][CH:19]=1)#[N:17]

Participants

6

Reactant 2

HCID 109119016-(5-Bromo-furan-2-yl)-nicotinonitrileHCID 178509808HCID 178509808, compound

Product 1

HCID 109460296-[5-(4-Cyanobenzyl)furan-2-yl]nicotinonitrileYield 48%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Continuing with Scheme 7, a solution of 2 (996 mg, 4 mmol) in tetrahydrofuran (25 mL) was added palladium tetrakis(triphenyl-phosphine) (228 mg) and p-cyanobenzyl zinc bromide (12 mL, 0.5 M in THF, 6 mmol). The reaction mixture was stirred 24 h at room temperature. The mixture was diluted with dichloromethane, washed with saturated NH4Cl and the organic layer was dried over anhydrous Na2SO4. After filtration and on concentration the residue was purified by chromatography (SiO2), hexanes (100–40%)/EtOAc (0–60%), to afford 35 in 48% yield, mp 204–206° C. 1H nmr (DMSO-d6); δ 4.23 (s, 2H), 6.46 (d, J=3.3 Hz, 1H), 7.27 (d, J=3.3 Hz, 1H), 7.51 (d, J=8.1 Hz, 2H), 7.77 (d, J=8.1 Hz, 2H), 7.79 (d, J=8.4 Hz, 1H), 8.25 (dd, J=8.4 Hz, 1.8 Hz, 1H), 8.92 (d, J=1.8 Hz, 1H). 13C nmr; δ 156.3, 152.6, 150.9, 150.6, 143.2, 140.5, 132.4, 129.6, 118.6, 117.5, 117.1, 113.5, 110.3, 109.5, 106.0, 33.5.

Workup

  1. washwashed with saturated NH4Cl
  2. dry with materialthe organic layer was dried over anhydrous Na2SO4
  3. filtrationAfter filtration
  4. concentrationon concentration the residue
  5. customwas purified by chromatography (SiO2), hexanes (100–40%)/EtOAc (0–60%)

Sources & evidence

ORD record
ord-d82fa10f2bd14f1898c50a99e4f7bac6
Source dataset
uspto-grants-2007_08
Patent number
US07256203B2

Reaction notes

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