2,4-DICHLORO-6-METHOXYQUINOLINE

2, 4-DICHLORO-6-METHOXYQUINOLINE. Phosphorus(V)oxychloride (40 mL, 1.5 M) was added through a condenser into a 3-neck round bottom flask containing malonic acid (6.244 g, 60.00 mmol) and a stir bar at room temperature. While stirring, p-anisidine (9.236 g, 75.00 mmol) was added in small portions over a period of 15 minutes through an open neck of the round bottom flask. The reaction mixture was heated and stirred at reflux for 5 hours. The reaction mixture was allowed to cool to room temperature before it was poured over crushed ice (700 mL). The pH of the resulting aqueous solution was then adjusted to 10 with concentrated ammonium hydroxide (85 mL). The aqueous suspension was extracted with dichloromethane. The combined organic layers were then dried over MgSOA mixture of p- anisidine (100 g, 0.813 mol), and malonic acid (85.0 g, 0.817 mol) in POCIA mixture of p- anisidine (100 g, 0.813 mol), and malonic acid (85.0 g, 0.817 mol) in POCl2, 4-DICHLORO-6-METHOXYQUINOLINE. Phosphorus(V)oxychloride (40 mL, 1.5 M) was added through a condenser into a 3-neck round bottom flask containing malonic acid (6.244 g, 60.00 mmol) and a stir bar at room temperature. While stirring, p-anisidine (9.236 g, 75.00 mmol) was added in small portions over a period of 15 minutes through an open neck of the round bottom flask. The reaction mixture was heated and stirred at reflux for 5 hours. The reaction mixture was allowed to cool to room temperature before it was poured over crushed ice (700 mL). The pH of the resulting aqueous solution was then adjusted to 10 with concentrated ammonium hydroxide (85 mL). The aqueous suspension was extracted with dichloromethane. The combined organic layers were then dried over MgSO4 before concentration. Purification by column chromatography (0-5percent ethyl acetate in hexanes) yielded the title compound as a slightly yellow solid (4.7812 g, 35percent). Mp 170.5-171.5° C.; Rf=0.27 (2percent EtOAc/hexanes); IR (film) 3084, 3013, 2982, 1623, 1562, 1499 cm-1; 1H NMR (500 MHz, CDCl3) delta 7.90 (d, J=9.0 Hz, 1H), 7.45 (s, 1H), 7.40 (dd, J=9.0, 3.0 Hz, 1H), 7.36 (d, J=3.0 Hz, 1H), 3.96 (s, 3H); 13C NMR (125 MHz, CDCl3) ppm 158.9, 147.0, 144.0, 142.6, 130.4 126.3, 124.1, 122.0, 101.9, 55.7; HRMS submitted.A mixture of p- anisidine (100 g, 0.813 mol), and malonic acid (85.0 g, 0.817 mol) in POCI3 (500 mL) was refluxed for 6 hours. The excess POCI3 was removed in vacuo and the residue was neutralized with 8 M NaOH to pH 7. The aqueous layer was extracted with CH2CI2 (300 mL x 3), washed with brine (500 mL), dried over Na2S04 and concentrated under reduced pressure. Purification by column chromatography on silica gel (PE / EtOAc = 15/1) gave desired (35.0 g, yield: 19percent).POC13 (80 ml) was added through a condenser into a 250 mL round bottom flask containing malonic acid (25.3 g, 244 mmol) at 20 °C. While stirring, 4-methoxyaniline (20 g, 162 mmol) was added in small portions over a period of 15 minutes. The reaction mixture was heated and stirred at 105 °C for 3 h. Thenthe reaction mixture was cooled to 20 °C and concentrated in vacuo to remove POC13. The resulting residue was dissolved in DCM (200 mL). Then the mixture was poured into concentrated ammonium hydroxide and the final pH of the aquesous layer was about 10. The aqueous layer was extracted with DCM (3 x 100 mL). The combined organic layers were dried over Na2504, filtered and concentrated in vacuo. The resulting residue was purified by columnchromatography (5i02, PE:EtOAc =100:1 to 10:1) to give the title compound.To a mixture of 2, 4- dichloro-

Molecular Weight:228.07
XLogP3:3.8
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:226.9904692
Monoisotopic Mass:226.9904692
Topological Polar Surface Area:22.1
Heavy Atom Count:14
Complexity:203
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes