Dimethylformamide → 4-Chloro-3-(tetrahydro-pyran-2-yloxymethyl)-pyridine-2-carbonitrile

HRID 1959600Notes

Reaction equation

HRID 1959600 reaction equation
Cl[C:2]1[C:7]([CH2:8][O:9][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][O:11]2)=[C:6]([Cl:16])[CH:5]=[CH:4][N:3]=1.[CH3:17][N:18](C=O)C>O.[C-]#N.[Zn+2].[C-]#N.[Zn].C([O-])(=O)C.[Zn+2].C([O-])(=O)C.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]>[Cl:16][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:17]#[N:18])[C:7]=1[CH2:8][O:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][O:11]1

Participants

8

Reactant 2

HCID 6228DimethylformamideHCID 86645362HCID 86645362, compound

Product 1

HCID 670775644-Chloro-3-(tetrahydro-pyran-2-yloxymethyl)-pyridine-2-carbonitrile

Reagents, catalysts & solvents 5

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11192Zinc AcetateCatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

2,4-Dichloro-3-(tetrahydro-pyran-2-yloxymethyl)-pyridine (455 mg. 1.74 mmol) was dissolved in a mixture of DMF (3 mL) and water (30 μL). The following reagents were added subsequently: zinc cyanide (112 mg. 0.95 mmol), zinc dust (9.1 mg. 139 μmol), zinc acetate (25.5 mg. 139 μmol). 1,1′-bis(diphenylphosphino)ferrocene (58 mg. 104 μmol) and tris(dibenzylideneacetone)palladium (0). The reaction mixture was degassed two times and afterwards heated at 95° C. for 4 h. The solvents were removed in vacuo and the residue was pardoned between water (20 mL) and EtOAc (20 mL) and extracted with EtOAc (3×20 ml). The combined organic layers were washed with brine and dried over Na2SO4 filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (elution with hexane/EtOAc 10:1→5:1) to give the title compound. MS (m/z): 253.0 [M+H+].

Workup

  1. additionThe following reagents were added subsequently
  2. customThe reaction mixture was degassed two times
  3. customThe solvents were removed in vacuo
  4. extractionextracted with EtOAc (3×20 ml)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography on silica gel (elution with hexane/EtOAc 10:1→5:1)

Sources & evidence

ORD record
ord-7cb16a4656344b03b88ce7122d259da3
Source dataset
uspto-grants-2013_04
Patent number
US08410134B2

Reaction notes

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