Ethyl Acetate → HCID 86636421, compound

HRID 1483670Notes

Reaction equation

HRID 1483670 reaction equation
Cl[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]=1.[Br:10][C:11]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][C:12]=1[CH:13]=[O:14].C([O-])([O-])=O.[K+].[K+].CCOC(C)=O>CN(C=O)C.O>[Br:10][C:11]1[CH:18]=[CH:17][C:16]([O:19][C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]=2)=[CH:15][C:12]=1[CH:13]=[O:14]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 3871792-Bromo-5-hydroxybenzaldehydeHCID 51520946-Chloro-3-pyridinecarbonitrile

Product 1

HCID 86636421HCID 86636421, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 6-chloro-nicotinonitrile (3.5 g, 25.0 mmol, 1.0 eq.), 2-bromo-5-hydroxy-benzaldehyde (5.0 g, 25.0 mmol, 1.0 eq.) in DMF (40.0 mL) was added K2CO3 (4.1 g, 30.0 mmol, 1.2 eq.) under nitrogen atmosphere. The mixture was heated at 80° C. overnight. After cooling to room temperature, the mixture was poured into EtOAc (30 mL) and H2O (30 mL). The layers were separated and the aqueous phase was extracted with EtOAc (3×20 mL). Combined organic extracts was washed with brine (30 mL), dried over MgSO4, filtered and the filtrate was concentrated under reduced pressure. The residue was applied to silica chromatography eluting with MeOH/DCM (0:100 to 10:90) to give 6-(4-bromo-3-formyl-phenoxy)-nicotinonitrile as a white solid. 1H NMR (CHLOROFORM-d) δ: 10.35 (s, 1H), 8.43 (dd, J=2.3, 0.6 Hz, 1H), 7.98 (dd, J=8.6, 2.3 Hz, 1H), 7.69-7.77 (m, 2H), 7.30 (dd, J=8.6, 3.0 Hz, 1H), 7.12 (dd, J=8.6, 0.8 Hz, 1H). Amount obtained, 5.92 g, 78% yield.

Workup

  1. temperatureAfter cooling to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted with EtOAc (3×20 mL)
  4. washCombined organic extracts was washed with brine (30 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. washeluting with MeOH/DCM (0:100 to 10:90)

Sources & evidence

ORD record
ord-a8853579e2db406291ffcc0029bc4426
Source dataset
uspto-grants-2016_08
Patent number
US09416146B2

Reaction notes

Loading…