Malonic Acid → 2,4,8-Trichloro-7-methoxyquinoline

Reaction equation

[ClH:1].[Cl:2][C:3]1[C:9]([O:10][CH3:11])=[CH:8][CH:7]=[CH:6][C:4]=1[NH2:5].[C:12](O)(=O)[CH2:13][C:14](O)=O.O(Cl)[Cl:20].[P]>O>[Cl:1][C:14]1[CH:13]=[C:12]([Cl:20])[C:6]2[C:4](=[C:3]([Cl:2])[C:9]([O:10][CH3:11])=[CH:8][CH:7]=2)[N:5]=1

Participants

Procedure

A mixture of 2-chloro-3-methoxyaniline hydrochloride 215d (15 g, 1 eq.), malonic acid (12.06 g, 1.5 eq.), and phosphorus oxochloride (80 mL) was refluxed for 16 hrs. The reaction mixture was slowly poured into water and extracted with DCM. The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified on silica pad, eluted with DCM, to yield compound 220d as a white solid in 74% yield. 1H NMR (CDCl3, 376 MHz) δ 4.10 (s, 3H), 7.43 (t, J=4.88 Hz, 2H), 8.12 (d, J=9.48 Hz, 1H).