Tetrahydrofuran → 7-chloro-3-methyl-1-phenyl-1H-quinolin-4-one

HRID 1887795Notes

Reaction equation

HRID 1887795 reaction equation
[CH2:1]1COCC1.C(Cl)(=O)C(Cl)=O.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:22])[CH2:20][CH3:21])=[C:15]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:14]=1>CN(C=O)C.O>[Cl:12][C:13]1[CH:14]=[C:15]2[C:16]([C:19](=[O:22])[C:20]([CH3:1])=[CH:21][N:23]2[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)=[CH:17][CH:18]=1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 65578Oxalyl chlorideHCID 708166141-(4-Chloro-2-phenylamino-phenyl)-propan-1-one

Product 1

HCID 712085227-chloro-3-methyl-1-phenyl-1H-quinolin-4-oneYield 81.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
115 °C

Procedure

To a mixture of THF (60 mL) and DMF (7.5 mL) at 0° C. under nitrogen was added oxalyl chloride (6.5 mL, 76.8 mmol) during which time a white precipitate formed. The temperature was slowly raised to room temp. and stirred for 1.5 hr. THF was distilled off from the reaction mixture under reduced pressure and under nitrogen. The gummy residue was further diluted with DMF (100 mL). A solution of 1-(4-chloro-2-phenylamino-phenyl)-propan-1-one (5.0 g, 19.30 mmol) in DMF (50 mL) was added to the reaction mixture at room temperature. The reaction was heated at 115° C. for 2 hr. The reaction mixture was brought down to room temperature, then diluted with water (750 mL), and the mixture was extracted with ethyl acetate (2×750 mL). The combined organic layers were washed with brine (500 mL), dried, and concentrated under reduced pressure to yield 7-chloro-3-methyl-1-phenyl-1H-quinolin-4-one (4.25 g, 81.6%) as an off-white solid. 1H NMR (DMSO-d6) δ ppm 8.24 (d, J=8.8 Hz, 1H) 8.01 (s, 1H) 7.52-7.80 (m, 5H) 7.40 (dd, J=8.8, 1.8 Hz, 1H) 6.87 (d, J=1.8 Hz, 1H) 2.01 (s, 3H). MS calcd. for C16H12ClNO [(M+H)+] 270.0, obsd. 269.8.

Workup

  1. customformed
  2. temperatureThe temperature was slowly raised to room temp.
  3. distillationTHF was distilled off from the reaction mixture under reduced pressure and under nitrogen
  4. additionThe gummy residue was further diluted with DMF (100 mL)
  5. customwas brought down to room temperature
  6. extractionthe mixture was extracted with ethyl acetate (2×750 mL)
  7. washThe combined organic layers were washed with brine (500 mL)
  8. customdried
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ae801396c3084387896de1bad2d0c3bd
Source dataset
uspto-grants-2013_08
Patent number
US08501732B2

Reaction notes

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