Dimethylformamide → 6-Quinolinecarboxaldehyde, 4-ethoxy-

HRID 852990Notes

Reaction equation

HRID 852990 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][CH2:13][CH3:14].C([Li])CCC.CN(C)[CH:22]=[O:23]>O1CCCC1.[Cl-].[NH4+]>[CH2:13]([O:12][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([CH:22]=[O:23])[CH:3]=2)[N:8]=[CH:7][CH:6]=1)[CH3:14]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 586153986-Bromo-4-ethoxyquinolineHCID 178418339Butyllithium

Product 1

HCID 586153616-Quinolinecarboxaldehyde, 4-ethoxy-Yield 88%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
-65 °C

Procedure

To a solution of 6-bromo-4-ethoxy-quinoline (0.53 g, 2.1 mmol) in THF (tetrahydrofuran) (21 mL) was added dropwise a 2.5M solution of n-butyllithium in hexanes (0.92 mL, 2.3 mmol, 1.1 equiv.) at −70° C. During the addition, the temperature of the reaction mixture was raised slightly to −65° C. and it gave a very dark brown solution. The resulting colored solution was stirred for 30 min at this temperature. Then, a solution of dimethylformamide (0.324 mL, 4.2 mmol) in THF (2 mL) was added dropwise. After addition, the mixture was allowed to warm to room temperature and stirred for 15 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 (3×50 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 brown solid which was purified by using a Biotage silica gel column chromatography to afford 0.370 g (88% yield) of 4-ethoxyquinoline-6-carbaldehyde as a white solid: EI-HRMS m/e calcd for C12H11NO2 (M+) 201.0790, found 201.0787

Workup

  1. additionDuring the addition
  2. customit gave a very dark brown solution
  3. additionAfter addition
  4. temperatureto warm to room temperature
  5. stirringstirred for 15 h
  6. customthe two layers were separated
  7. extractionThe aqueous layer was extracted with ethyl acetate (3×50 mL)
  8. washThe combined organic extracts were washed with brine solution
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationFiltration of the drying agent and removal of the solvent under the vacuum
  11. customgave the crude brown solid which
  12. customwas purified

Sources & evidence

ORD record
ord-63c377bb76e24aea9e74bcd436f86800
Source dataset
uspto-grants-2007_08
Patent number
US07253285B2

Reaction notes

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