反应详情

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.

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