Diethyl Ether → 2-Cyano-5-fluoropyridine

HRID 450353Notes

Reaction equation

HRID 450353 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.CCOCC.C[C:15]([N:17](C)C)=O>[Cl-].[Na+].O.[Zn].[C-]#N.[Zn+2].[C-]#N.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:8][C:5]1[CH:6]=[CH:7][C:2]([C:15]#[N:17])=[N:3][CH:4]=1

Participants

9

Reactant 3

HCID 3283Diethyl EtherHCID 31374DimethylacetamideHCID 27831712-Bromo-5-fluoropyridine

Product 1

HCID 113324532-Cyano-5-fluoropyridineYield 72%

Reagents, catalysts & solvents 5

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 57417360Sodium chloride; waterSolvent

Procedure

2-Bromo-5-fluoropyridine (93.0 g, 528 mmol), Zn dust (8.29 g, 127 mmol), zinc cyanide (40.3 g, 343 mmol), 1,1′-bis(diphenylphosphino)ferrocene (11.7 g, 21.1 mmol) and Pd2dba3 (9.68 g, 10.6 mmol) in anhydrous DMAc (300 ml) was heated at 95° C. for 3 hours. After cooled to room temperature, brine (100 ml) and ether (500 ml) was added. The solid formed was removed by filtration and washed with ether (300 ml). The organic layer was separated, washed with brine (200 ml) and dried over sodium sulfate, and concentrated. After removal of solvent, the resulted residue was purified by column chromatography (hexane-DCM=1:1) to give the title compound as a white solid (49 g, 72%). 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J=2.8 Hz, 1H), 8.21 (dd, J=4.4 and 8.8 Hz, 1H), 8.05 (dd, J=2.8 and 8.8 Hz, 1H).

Workup

  1. customThe solid formed
  2. customwas removed by filtration
  3. washwashed with ether (300 ml)
  4. customThe organic layer was separated
  5. washwashed with brine (200 ml)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customAfter removal of solvent
  9. customthe resulted residue was purified by column chromatography (hexane-DCM=1:1)

Sources & evidence

ORD record
ord-b1ade2fa177d4895b40fcb1c3d2499eb
Source dataset
uspto-grants-2013_07
Patent number
US08486966B2

Reaction notes

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