Dimethylformamide → 6-Quinolinecarboxaldehyde, 4-phenoxy-

HRID 853004Notes

Reaction equation

HRID 853004 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[C:5]2[O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C([Li])CCC.CN(C)[CH:26]=[O:27]>C1COCC1.[Cl-].[NH4+]>[O:12]([C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([CH:26]=[O:27])[CH:3]=2)[N:8]=[CH:7][CH:6]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 58615386HCID 58615386, compoundHCID 178418339Butyllithium

Product 1

HCID 586153566-Quinolinecarboxaldehyde, 4-phenoxy-Yield 27%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of 6-bromo-4-phenoxy-quinoline (1.12 g, 3.73 mmol) in THF (15 mL) was added dropwise a 2.5M solution of n-butyllithium in hexanes (1.64 mL, 4.10 mmol, 1.1 equiv.) at −70° C. During the addition, the color of the solution was turned into brown and this solution was stirred for 20 min at this temperature. Then, a neat dimethylformamide (0.576 mL, 7.46 mmol) was added dropwise. After addition, the mixture was allowed to warm to room temperature and stirred for 2 h. Then, the mixture was diluted with saturated ammonium chloride solution and the two layers were separated. The aqueous layer was extracted with ethyl acetate (2×75 mL). The combined organic extracts were washed with brine solution and dried over anhydrous magnesium sulfate. Filtration of the drying agent and removal of the solvent under the vacuum gave the crude residue which was purified by using a Biotage silica gel column chromatography to afford 0.250 g (27% yield) of 4-phenoxy-quinoline-6-carbaldehyde as a white solid: mp 112-115° C.; EI-HRMS m/e calcd for C16H11NO2 (M+) 249.0790, found 249.0787.

Workup

  1. additionDuring the addition
  2. additionAfter addition
  3. stirringstirred for 2 h
  4. customthe two layers were separated
  5. extractionThe aqueous layer was extracted with ethyl acetate (2×75 mL)
  6. washThe combined organic extracts were washed with brine solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationFiltration of the drying agent and removal of the solvent under the vacuum
  9. customgave the crude residue which
  10. customwas purified

Sources & evidence

ORD record
ord-80fb0828b6b049b7aa8e42844dbb10df
Source dataset
uspto-grants-2007_08
Patent number
US07253285B2

Reaction notes

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