Ethyl Acetate → 5-(Benzyloxy)nicotinonitrile

HRID 526372Notes

Reaction equation

HRID 526372 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[N:11][CH:12]=[C:13](Br)[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cu](C#N)[C:17]#[N:18].C(=O)([O-])O.[Na+].C(OCC)(=O)C>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([C:17]#[N:18])[CH:12]=[N:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 153891983-(Benzyloxy)-5-bromopyridineHCID 178418260HCID 178418260, compound

Product 1

HCID 538508325-(Benzyloxy)nicotinonitrileYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

3-(Benzyloxy)-5-bromopyridine (5.38 g, 20.4 mmol, Harrowven et al. Tetrahedron, 2001, 57, 4447-4454) in DMF (33 mL) was stirred with copper cyanide (2.9 g, 32.6 mmol) at 160° C. for 7 hours. Saturated aqueous sodium hydrogen carbonate solution and ethyl acetate was added and the formed suspension was stirred at 50° C. for 15 minutes. After filtration the liquid phases were separated. The precipitate was triturated with 10% DMF in ethyl acetate (500 mL) and saturated aqueous sodium hydrogen carbonate solution (100 mL) at 50° C. and filtration and phase separation were performed. The treatment of the precipitate with saturated aqueous sodium hydrogen carbonate solution and 10% DMF in ethyl acetate was repeated two times and the combined organic phases washed with brine and dried over sodium sulfate. The solution was concentrated under reduced pressure and the residue was purified by chromatography on silica gel (ethyl acetate in hexane, 0 to 65%) to yield 3.13 g 5-(benzyloxy)pyridine-3-carbonitrile.

Workup

  1. filtrationAfter filtration the liquid phases
  2. customwere separated
  3. customThe precipitate was triturated with 10% DMF in ethyl acetate (500 mL) and saturated aqueous sodium hydrogen carbonate solution (100 mL) at 50° C.
  4. filtrationfiltration and phase separation
  5. washthe combined organic phases washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationThe solution was concentrated under reduced pressure
  8. customthe residue was purified by chromatography on silica gel (ethyl acetate in hexane, 0 to 65%)

Sources & evidence

ORD record
ord-ec2079e23e534feb92e2b2ae838d08a9
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

Loading…