4-Hydroxybenzaldehyde → 6-(4-Formylphenoxy)nicotinonitrile

HRID 228496Notes

Reaction equation

HRID 228496 reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.Cl[C:11]1[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][N:12]=1.C([O-])([O-])=O.[K+].[K+].CC(N(C)C)=O.C1(C)C=CC=CC=1>C(OCC)(=O)C>[CH:6]([C:5]1[CH:8]=[CH:9][C:2]([O:1][C:11]2[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][N:12]=2)=[CH:3][CH:4]=1)=[O:7]

Participants

6

Reactant 4

HCID 1264-HydroxybenzaldehydeHCID 11430Potassium CarbonateHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 66603805toluene N,N-dimethylacetamide

Product 1

HCID 471502166-(4-Formylphenoxy)nicotinonitrileYield 89.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Combine 4-Hydroxybenzaldehyde (8.0 g, 65.5 mmol), 6-Chloronicotinonitrile (9.07 g, 65.5 mmol), powdered K2CO3 (13.6 g, 98.3 mmol), and DMA/Toluene (80/240 mL) in a 500 mL RB flask equipped with a stir, reflux condenser and a Dean Stark Trap. Reflux the reaction mixture for several hours under a Nitrogen atmosphere then cool to room temperature and quench with sat NH4Cl (aq). Add Ethyl acetate to extract the product and wash several times with water and then brine. Dry the organic layer over Na2SO4. Concentrate and flash chromatograph using 2:1 Hexanes:Ethyl acetate to give 13.2 g (88% yield) of the title compound: 1H NMR (500 MHz, CDCl3); 7.1 (1H, d), 7.3-7.4 (2H, m), 7.9-8.0 (3H, m), 8.5 (1H, d), 10.0 (1H, s); MS m/z 225 (M+1).

Workup

  1. temperaturereflux condenser
  2. temperatureReflux the reaction mixture for several hours under a Nitrogen atmosphere
  3. customquench with sat NH4Cl (aq)
  4. extractionAdd Ethyl acetate to extract the product
  5. washwash several times with water
  6. dry with materialDry the organic layer over Na2SO4
  7. concentrationConcentrate

Sources & evidence

ORD record
ord-9aed9d76c31741ec977db8b707c2878d
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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