Dimethyl acetylenedicarboxylate → 5-Bromo-2-fluoropyridine-3-carbonitrile

HRID 55859Notes

Reaction equation

HRID 55859 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[N:10]O)[C:5]([F:8])=[N:6][CH:7]=1.COC(C#CC(OC)=O)=O>CC#N>[Br:1][C:2]1[CH:7]=[N:6][C:5]([F:8])=[C:4]([CH:3]=1)[C:9]#[N:10]

Participants

4

Reactant 2

HCID 12980Dimethyl acetylenedicarboxylateHCID 1317368795-Bromo-2-fluoro-3-pyridinecarboxaldehyde oxime

Product 1

HCID 848197325-Bromo-2-fluoropyridine-3-carbonitrileYield 69%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 5-Bromo-2-fluoro-pyridine-3-carbaldehyde oxime (3) (19.0 g, 86.8 mmol) in MeCN (400 mL) was added dimethylacetylene dicarboxylate (25.0 g, 176 mmol) and TEA (24.1 mL, 173 mmol) dropwise. The reaction mixture was stirred at rt for 4 hours. The solvent was evaporated in vacuo and the residue diluted with CHCl3 (300 mL) and H2O (300 mL). The layers were separated and the organic phase washed with saturated brine solution (200 mL), then dried (Na2SO4), filtered and the solvent evaporated in vacuo. The crude product was purified by column chromatography (100-200 mesh silica gel, 10% EtOAc-pet ether) to provide the title compound as a white solid (12.0 g, 69%); Rf: 0.7 (20% EtOAc-pet ether).

Workup

  1. customThe solvent was evaporated in vacuo
  2. additionthe residue diluted with CHCl3 (300 mL) and H2O (300 mL)
  3. customThe layers were separated
  4. washthe organic phase washed with saturated brine solution (200 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customthe solvent evaporated in vacuo
  8. customThe crude product was purified by column chromatography (100-200 mesh silica gel, 10% EtOAc-pet ether)

Sources & evidence

ORD record
ord-6b26f7668aae41deb5a07de6cbfb8961
Source dataset
uspto-grants-2016_09
Patent number
US09433622B2

Reaction notes

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