Ethyl Acetate → (6-Bromo-4-chloro-7-fluoroquinolin-3-yl)(cyclopropyl)methanone

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[N:8]=[CH:7][C:6]([C:13]([CH:15]1[CH2:17][CH2:16]1)=[O:14])=[C:5]2O.[OH-].[NH4+].C(OCC)(=O)C.P(Cl)(Cl)([Cl:29])=O>>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[N:8]=[CH:7][C:6]([C:13]([CH:15]1[CH2:17][CH2:16]1)=[O:14])=[C:5]2[Cl:29]

Participants

Reactant 4

HCID 8857Ethyl Acetate

HCID 14923Ammonium Hydroxide

HCID 24813Phosphorus oxychloride

HCID 178519813HCID 178519813, compound

Product 1

HCID 66715407(6-Bromo-4-chloro-7-fluoroquinolin-3-yl)(cyclopropyl)methanoneYield 42%

Procedure

(6-Bromo-7-fluoro-4-hydroxyquinolin-3-yl)(cyclopropyl)methanone (3.35 g, 10.8 mmol) was suspended in phosphoryl chloride (10 mL) at 0° C. The reaction was warmed to room temperature and stirred overnight. After this time 2M ammonium hydroxide was added dropwise until a solid formed. Ethyl acetate was added and the layers were separated. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to afford the desired product (1.5 g, 42%) as an off-white solid: 1H NMR (300 MHz, CDCl3) δ 8.92 (s, 1H), 8.63 (d, J=7.2 Hz, 1H), 7.84 (d, J=8.9 Hz, 1H), 2.70-2.45 (m, 1H), 1.55-1.35 (m, 2H), 1.35-1.05 (m, 2H).