HCID 90204301, compound → HCID 90204051, compound

HRID 1480187Notes

Reaction equation

HRID 1480187 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[CH:4][C:3]=1[C:9]1([OH:13])[CH2:12][O:11][CH2:10]1.[C:14]([Zn]C#N)#[N:15]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[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]>[Cl:1][C:2]1[C:3]([C:9]2([OH:13])[CH2:12][O:11][CH2:10]2)=[CH:4][N:5]=[C:6]([C:14]#[N:15])[CH:7]=1

Participants

6

Reactant 2

HCID 90204301HCID 90204301, compoundHCID 178514179HCID 178514179, compound

Product 1

HCID 90204051HCID 90204051, compoundYield 155.7%

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-(4,6-dichloropyridin-3-yl)oxetan-3-ol (example 123a, 5.0 g, 22.7 mmol) in dry DMF (100 ml) under argon atmosphere was added dicyanozinc (1.47 g, 12.5 mmol), DPPF (1.26 g, 2.27 mmol) and Pd2(dba)3 (1.04 g, 1.14 mmol). The reaction mixture was then stirred at 100° C. for two hours. DMF was removed in vacuo and the obtained residue was dissolved in ethyl acetate and poured into a separatory funnel. The organic phase was extracted with a saturated solution of ammonium chloride (colloids formed and were removed by filtration on a pad of celite). The organic phase was collected and the aqueous phase was back-extracted with ethyl acetate. Combined organic phases were dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a heptane/ethyl acetate gradient to yield the title compound (4.1 gr, 86%); MS (ESI, m/z): 211.1 (M+H+).

Workup

  1. customDMF was removed in vacuo
  2. dissolutionthe obtained residue was dissolved in ethyl acetate
  3. additionpoured into a separatory funnel
  4. extractionThe organic phase was extracted with a saturated solution of ammonium chloride (colloids
  5. customformed
  6. customwere removed by filtration on a pad of celite)
  7. customThe organic phase was collected
  8. extractionthe aqueous phase was back-extracted with ethyl acetate
  9. dry with materialCombined organic phases were dried over sodium sulfate
  10. customevaporated down to dryness
  11. customThe crude material was purified by flash chromatography on silica eluting with a heptane/ethyl acetate gradient

Sources & evidence

ORD record
ord-dcbddfcb1f354dcc8f0dc19bf45b5146
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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