Phosphorus oxychloride → Ethyl 4-chloro-6-methoxyquinoline-3-carboxylate

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][C:7]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:6]2O.O=P(Cl)(Cl)[Cl:21].P(Cl)(Cl)(Cl)(Cl)Cl>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][C:7]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:6]2[Cl:21]

Participants

Procedure

To a stirred solution of the crude 6-methoxy-4-hydroxy-3-ethoxycarbonylquinoline (Step A, 74 g, 0.25 M) in dry toluene (300 mL) was added POCl3 (46.6 mL, 0.5 mol) followed by PCl5 (26 g, 0.125 mol). The mixture was heated at reflux for 6 h. The toluene and the excess of POCl3 were removed under vacuum. The solid residue was suspended into a mixture of 1N NaOH and ice. The resulting solid was filtered off, washed several times with water, then with a minimum amount of MeOH, and dried over P2O5 to give 6-methoxy-4-chloro-3-ethoxycarbonylquinoline as a white solid.