Toluene → 7-Chloro-3-(4-methoxycarbonyl-benzyl)-4-oxo-1-phenyl-1,4-dihydro-quinoline-2-carboxylic acid methyl ester

HRID 1261755Notes

Reaction equation

HRID 1261755 reaction equation
[CH3:1][O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][C:12]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:13])=[CH:6][CH:5]=1.C1(C)C=CC=CC=1.Cl[C:37](=O)[C:38]([O:40][CH3:41])=[O:39]>O>[CH3:41][O:40][C:38]([C:37]1[N:21]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:15]2[C:14]([C:12](=[O:13])[C:11]=1[CH2:10][C:7]1[CH:6]=[CH:5][C:4]([C:3]([O:2][CH3:1])=[O:28])=[CH:9][CH:8]=1)=[CH:19][CH:18]=[C:17]([Cl:20])[CH:16]=2)=[O:39]

Participants

5

Reactant 3

HCID 1140TolueneHCID 79846Methyl chloroglyoxylateHCID 70817153Methyl 4-(3-(4-chloro-2-(phenylamino)phenyl)-3-oxopropyl)benzoate

Product 1

HCID 598461727-Chloro-3-(4-methoxycarbonyl-benzyl)-4-oxo-1-phenyl-1,4-dihydro-quinoline-2-carboxylic acid methyl esterYield 53.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 1 L round-bottomed flask equipped with a magnetic stir bar, a water cooled reflux condenser, a nitrogen bubbler and a thermometer was charged with 4-[3-(4-chloro-2-phenylamino-phenyl)-3-oxo-propyl]-benzoic acid methyl ester (54 g, 137 mmol), toluene (2 L, 18.8 mol) and methyl 2-chloro-2-oxoacetate (200 mL, 2.17 mol). The resulting mixture was heated to reflux overnight. At this time, the reaction mixture was concentrated to a thick gum. This residue was dissolved in methanol (1 L), treated with potassium carbonate (31 g) and stirred overnight. At this time, the reaction was filtered to remove solids. The filtrate was treated with acetic acid (50 mL) and then concentrated in vacuo. The residue was absorbed onto silica gel. Flash chromatography (2″×6″ column; 50-66% ethyl acetate/hexanes) followed by concentration of the appropriate fractions produced a solid. This solid was slurried with 1:1 ethyl acetate/hexanes, collected by filtration and dried in vacuo to afford 7-chloro-3-(4-methoxycarbonyl-benzyl)-4-oxo-1-phenyl-1,4-dihydro-quinoline-2-carboxylic acid methyl ester (34 g, 53.7%) as an off-white solid. This material was used without further purification.

Workup

  1. customA 1 L round-bottomed flask equipped with a magnetic stir bar
  2. temperaturereflux condenser
  3. temperatureThe resulting mixture was heated
  4. temperatureto reflux overnight
  5. concentrationAt this time, the reaction mixture was concentrated to a thick gum
  6. dissolutionThis residue was dissolved in methanol (1 L)
  7. additiontreated with potassium carbonate (31 g)
  8. filtrationAt this time, the reaction was filtered
  9. customto remove solids
  10. additionThe filtrate was treated with acetic acid (50 mL)
  11. concentrationconcentrated in vacuo
  12. customThe residue was absorbed onto silica gel
  13. customproduced a solid
  14. filtrationcollected by filtration
  15. customdried in vacuo

Sources & evidence

ORD record
ord-4a302874b9b64fa3a7179c9130430408
Source dataset
uspto-grants-2013_06
Patent number
US08471027B2

Reaction notes

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